Metabolic / Nutritional / Toxic / Radiation Myelopathies

Disease/Disorder

Definition

These myelopathies encompass a heterogeneous group of disorders affecting the spinal cord, often with concurrent involvement of the brain and peripheral nerves. Despite varying etiologies, these conditions share clinical, electrophysiological, and neuropathological features, allowing for unified classification. For example, nutritional myelopathies frequently overlap with metabolic mechanisms.

The dorsal columns are typically most affected, though corticospinal tract and peripheral nerve involvement are common – prompting the alternative term “myeloneuropathy.”

Classification

These myelopathies can be stratified into the following categories

• Nutrient deficiency and metabolic myelopathies – Caused by deficiencies in vitamin B12, vitamin E, folate, or copper.
• Toxic and drug-induced myelopathies – Associated with substances such as heroin, cancer-related treatments (chemotherapeutic agents, radiation therapy, or immunotherapy) or other neurotoxins.
• Geographically linked myelopathies – Resulting from regional dietary habits (e.g., lathyrism, konzo) or environmental exposures (e.g., clioquinol toxicity, fluorosis, radiation in endemic regions).

Etiology

Nutrient deficiency and metabolic myelopathies 

The most common cause of nutritional myelopathy is B12 deficiency. It can cause myelopathy, neuropathy, and neuropsychiatric disturbances. In manifests as a subacute combined degeneration in the spinal cord. Subacute combined degeneration was first described in 1884. Folate, copper, and vitamin E deficiency also cause myelopathies.

Hepatic dysfunction can be associated with myelopathy, particularly in those with portosystemic shunts, thought to be the result of ammonia or elevated manganese.

In the case of bariatric surgery, the postoperative period can be complicated by both nutritional deficiencies along with a systemic stress response induced by the catabolic weight loss phase, in which new-onset myelopathies can commonly appear.¹

Genetic conditions, which may present as a metabolic myelopathy, often with other central nervous system involvement, include adult polyglucosan body disease, adrenomyeloneuropathy and other leukodystrophies, spinal xanthomatosis, biotinidase deficiency, arginase deficiency, mitochondrial disorders, and hexosaminidase A deficiency.

Toxic and drug-induced myelopathies 

Some myelopathies can result from toxins, such as nitrous oxide or heroin.

There are many drugs and chemical agents that cause myelopathy or myeloneuropathy. These include clioquinol, organophosphate, and chemotherapeutic agents, such as cisplatin, intrathecal methotrexate, and anti-TNF medications. Clioquinol use, mainly in Japan (removed from the market in 1970), was responsible for a disorder called subacute myelo-opticoneuropathy. This is composed of visual loss, lower limb sensory loss, bowel and bladder dysfunction and gait abnormalities.

Chemotherapy and radiation treatment for both primary and metastatic tumors can induce myelopathy. Several chemotherapeutic agents have been associated with acute myelopathy, including methotrexate, cytarabine, cisplatin, cladribine, doxorubicin, vincristine, and cytosine arabinoside.

Radiation-induced myelopathy represents a rare but serious complication of radiation therapy. To mitigate this risk, strict dose limitations are maintained when irradiating the spinal cord, with careful adherence to established tolerance thresholds. The diagnosis of radiation myelopathy is typically made clinically and remains one of exclusion, requiring comprehensive evaluation and imaging to differentiate it from disease progression, new metastases, or other neurologic complications.

This condition may develop following radiation exposure to the spinal cord during treatment of primary or metastatic spinal tumors, or during therapy for adjacent malignancies such as lymphoma or mediastinal tumors. Clinically, radiation myelopathy may manifest as either an early, often transient form appearing weeks to months post-treatment, or as a more concerning delayed progressive variant.

Geographically linked myelopathies 

Other myelopathies are the result of toxins that have a geographic predilection, such as lathyrism. The cause of lathyrism is ingestion of a toxic amino acid contained in the grass (chickling) pea, Lathyrus sativus. It is found across India, Bangladesh, and Ethiopia. and causes an acute to subacute, irreversible, nonprogressive spastic paraparesis that may be preceded by a series of symptoms including lower limb weakness, myalgia and stiffness.  The last recorded episode of the disease is from Ethiopia during the 1995-1997 famine, and in India it has virtually disappeared during the last three decades despite its continued cultivation and consumption in several areas. Even during the recent Ethiopian famine the disease was well controlled by the timely introduction of food aid cereal supplementation. What has become abundantly clear over the years is the fact that as part of a normal diet like most legumes Lathyrus sativus appears to be well tolerated and is only an issue during times of famine as evidenced by the virtual disappearance of the disease from India during the past three decades.

Konzo is another common toxic myelopathy linked to high exposure to cyanogenic compounds in diets containing insufficiently processed bitter cassava (Manihot esculenta). It most often occurs across Africa with prolonged consumption of cassava root in conjunction with a diet deficient in protein, in particular, sulfur containing amino acids. These conditions are often precipitated by drought and famine. The result is an irreversible, nonprogressive spastic paraparesis. The onset is abrupt, less than 1 week, is symmetric and can be associated with bilaterally increased ankle jerks. Sensory loss and genitourinary impairment do not occur. Optic neuropathy occurs in about half the patients with this condition.

Fluorosis occurs when large amounts of fluoride are consumed.  This usually occurs when it is naturally present in the earth and water. Deposition of the fluoride occurs in bones with a predilection for the vertebral column. Neurologic symptoms are delayed and are seen in ~ 10% of patients with skeletal fluorosis with cord compression and less often radiculopathy.

Epidemiology including risk factors and primary prevention

Risk factors for these conditions are as diverse as the conditions themselves. Primary prevention consists of maintaining normative levels of key nutrients and avoiding drugs and other toxins if possible. For vitamin B12 deficiency with subacute combined degeneration, risk factors include malabsorptive disorders, such as poor nutrition, atrophic gastritis, celiac sprue, and gastric or ileal resections or bypass (such as Roux-en-Y), overgrowth of intestinal bacteria in blind loops, anastomoses, diverticula. It can also be caused by the use of drugs, such as H2 antagonists and metformin. It is less commonly seen in lactovegetarians, infants nursed by mothers deficient in vitamin B12, and individuals exposed to excessive amounts of nitrous oxide.

Folate deficiency is caused by alcoholism, gastrointestinal disease, folate antagonists (eg, methotrexate), or errors of folate metabolism. Cooper is an ubiquitous element present in most diets. However, copper deficiency can be seen in zinc excess, gastric bypass surgery, total parenteral nutrition, or enteral feeding. It is important to note that denture adhesive and topical zinc products may be an overlooked source of zinc excess in some patients. Vitamin E deficiency can be caused by chronic cholestasis, pancreatic insufficiency, gastrointestinal disease, or lipoprotein disorders; it is rarely as a result of dietary inadequacy. Hereditary disorders of vitamin E metabolism should especially be on the differential in children without signs of GI disease.

Epidemiology varies with the toxins as previously described. Risk factors for toxic myelopathies are exposures to the etiologic toxin. In the case of nitrous oxide toxicity, pre-existing B12 deficiency increases the risk of nitrous oxide myelopathy with exposure. For chemotherapy and radiation myelopathy, increased risk may be dose dependent and increase with higher doses, previous exposures, and even age.

Obesity independently, for reasons that remain unclear, can be associated with nutrient deficiencies which can be a risk for myelopathy.²

Patho-anatomy/physiology

Although the pathophysiology of the other toxic and metabolic myelopathies have not been as well described, some distinguishing factors do exist to help differentiate between the causes.

Nutrient deficiency and metabolic myelopathies 

Metabolic myelopathies are caused by nutritional deficiencies that are required for myelin and axon integrity and maintenance.¹ The most common and well-studied pathology is that of subacute combined degeneration (caused by B12 deficiency). The biochemical pathways in which vitamin B12 (cobalamin) are involved are complex. The neurologic manifestations are thought to be the result of impairment in the methylation of homocysteine to methionine, a reaction which depends on a cobalamin-dependent enzyme. The pathologic process is diffuse, uneven degeneration of the white matter of the spinal cord (and occasionally the brain). The earliest histologic event is swelling of the myelin sheaths, followed by a coalescence of small foci of tissue destruction into larger ones, imparting a vacuolated, sieve-like appearance to the tissue. Gliosis becomes pronounced in chronic lesions. These changes begin in the posterior columns of the lower cervical and upper thoracic segments and spread throughout the white matter. Nitrous oxide also leads to vitamin B12 deficiency because it inactivates vitamin B12 by oxidizing methylcobalamin, the active form of intracellular B12.

Toxic and drug-induced myelopathies 

The mechanism for heroin myelopathy is not well established, but several theories exist. The most promising theory is an immune-mediated hypersensitivity response as most cases of heroin myelopathy occur after a single use of heroin following a period of abstinence.

The mechanisms of chemotherapeutic agents and their effects on the pathogenesis of myelopathy is not fully understood but may be related back to B12 and folate deficiency and similar mechanisms or disruption of the endothelial cells and vascular permeability.

Radiation-induced damage to the nervous system progresses through a continuous cascade of interrelated pathological processes. At the cellular level, radiation triggers increased reactive oxygen species (ROS) and oxidative stress, disrupting the blood-spinal cord barrier through endothelial cell apoptosis and vascular permeability. These changes lead to secondary demyelination, ischemia, and inflammation, culminating in fibrosis and irreversible spinal cord dysfunction.^2-4

Clinically, the disease manifests in two temporal patterns:

1. Early-onset myelopathy (6 weeks – 6 months post-radiation)
   • Primarily involves transient demyelination, especially in the posterior columns.
   • Linked to acute ROS-mediated damage and blood-spinal cord barrier disruption.
2. Delayed myelopathy (>6 months post-radiation)
   • Features permanent structural damage, including vascular thrombosis, infarction, and progressive white matter degeneration.
   • Driven by chronic microvascular injury, fibrosis, and neuronal loss.

The risk of myelopathy exhibits a strong dose-response relationship, with significantly higher incidence at spinal cord doses >45–50 Gy or with larger irradiated volumes.^2-4

Geographically linked myelopathies 

In Lathyrism, the neurotoxic, β-N-oxalyl-L-α,β-diaminopropionic acid,  is present in in the grass (chickling) pea, Lathyrus sativus. In results in increased intracellular levels of reactive oxygen series and impairment of the mitochondrial oxidative phosphorylation chain.

Konzo is caused by high levels of dietary cyanide poisoning.

Clioquinol toxicity is an antifungal-antiprotozoal drug used to treat intestinal parasitic diseases in Japan from 1955-1970.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Most of these conditions have a subacute symptom onset; the exceptions include nitrous oxide toxicity and heroin myelopathy. Cassava toxicity, a result of weeks or even years of ingestion of cassava, can result in either an acute nonprogressive myelopathy or a slowly progressive disease characterized by ataxia, peripheral neuropathy, and optic atrophy.

Generally, although there may be improvement in some of these conditions with the appropriate treatment, the more common result is an irreversible but non-progressive process after identification.

Specific secondary or associated conditions and complications

In any of these conditions, gait abnormalities include a sensory ataxia, which may occur in association with spasticity, loss of joint position sense, and pathologic reflexes. Bowel, bladder, and sexual dysfunction may occur.

Copper deficiency myelopathy causes a sensory ataxia similar to subacute combined degeneration can also be accompanied by an optic neuropathy.

Vitamin E deficiency myelopathy causes a spinocerebellar syndrome and peripheral neuropathy. It is also associated with ophthalmoplegia, myopathy and retinopathy.

Heroin myelopathy causes a transverse myelitis and is often associated with rhabdomyolysis and urinary retention.

Radiation-induced myelopathy manifests in two distinct temporal patterns with differing prognoses. The early-onset form, developing within 6 weeks – 6 months months post-radiation, often presents with transient neurological symptoms. A classic feature is Lhermitte’s sign, electric shock-like paresthesias radiating down the spine and extremities upon neck flexion. This benign, self-limiting condition typically resolves completely within 2-9 months without progressing to permanent myelopathy.

In contrast, delayed radiation myelopathy emerges after a latent period of >6 months and carries a more ominous prognosis. This progressive form frequently results in irreversible neurological deficits due to permanent spinal cord damage. While significantly rarer than the transient early variant, delayed myelopathy often leads to lasting disability.

Essentials of Assessment

History

History should be comprehensive and include recent illnesses, dietary habits, travel, occupational and environmental exposures, and a general medical, surgical, and oncological history. It is worth noting if any family members are reporting similar symptoms. Neurologic symptoms should be elucidated, including motor and sensory abnormalities, problems with balance, proprioception, coordination, cognition, and spasticity. Identification of autonomic dysfunction, including changes in blood pressure and heart rate, as well as other symptoms including bowel, bladder, and sexual dysfunction is essential as well. Time course and speed of progression of symptoms should be noted. It is also important to screen for psychiatric manifestations such as depression and psychosis.

Physical examination

In addition to a general physical examination, a complete neurologic examination should be performed, including assessment of cognition, cranial nerves, motor, sensory (light touch, pinprick, vibration, joint position sense), reflexes, range of motion, spasticity, and coordination. Skin should be examined to look for pressure sores, and rectal examination should be performed to guide in assessment of injury and bowel/bladder management. Gait should also be assessed.

Functional assessment

Assessment of function, including activities of daily living (ADLs), mobility, and cognitive function should be similar to other types of nontraumatic myelopathy. A variety of scales can be used, including the Functional Independence Measure, the WeeFIM for children, the Spinal Cord Independence Measure, and/or the Walking Index for Spinal Cord Injury. Cognition can be screened using the Mini-Mental Status Examination.

Laboratory studies

Tests may include the following^5-6

• Vitamin B12 deficiency: serum vitamin B12 (cobalamin), serum methylmalonic acid, plasma total homocysteine, hematologic tests, Schilling test, serum gastrin, intrinsic factor, and parietal cell antibodies.
• Folate deficiency: serum folate, red blood cell folate (measures tissue stores), and plasma total homocysteine.
• Copper deficiency: serum and urine copper, serum ceruloplasmin, serum and urine zinc, and hematologic tests.
• Vitamin E deficiency: serum vitamin E, ratio of serum vitamin E to sum of serum cholesterol and triglycerides.
• Hepatic myelopathy: elevated serum manganese, liver function tests, and serum ammonia.
• Nitrous oxide toxicity: low serum B12 in the setting of nitrous oxide exposure, serum methylmalonic acid, plasma total homocysteine.
• Intrathecal chemotherapy: low serum folate (with intrathecal methotrexate-associated neurotoxicity).
• Cassava toxicity: serum thiocyanate as a biomarker for dietary cyanide exposure.
• Fluorosis: osteosclerosis and ligamentous calcification seen on x-ray with elevated alkaline phosphatase and parathyroid hormone with normal calcium and phosphorus levels. Urinary fluoride levels are not reliable.
• Genetic tests when appropriate. If a patient presents with what appears as a metabolic myelopathy but cannot find the source, they may have a hereditary myelopathy such as spinocerebellar ataxia, a motor neuron disease, leukodystrophies, or distal motor sensory axonopathies.⁷

Imaging

For all cases of acute myelopathy, CT scan is first recommended to ensure bony stability. MRI imaging is most useful when bony instability is not found on CT and further investigation needs to be done. For any myelopathy, acute or chronic, MRI can identify any extrinsic compression of the spinal cord that may be contributing to symptoms and could potentially be reversed. For these reasons, MRI is often performed early in the diagnostic course to determine etiology, severity, and location of spinal cord involvement. In cases of chronic nontraumatic myelopathy, the addition of IV contrast is recommended since the differential diagnosis is so wide. It is worth noting that some conditions can have symptoms that localize to a particular region of the spinal cord but are actually being mimicked by more proximal lesions.⁸

Magnetic resonance imaging (MRI) findings are similar in many of the nutritional myelopathies, including vitamin B12 deficiency myelopathy, nitrous oxide intoxications, and copper deficiency myelopathy. Typically, T2 signal hyperintensities are seen in the posterior and lateral columns, especially the cervical and upper thoracic extending over several segments. This signal has been referred to as an “inverted V sign”. Nitrous oxide toxicity will result in the same pattern. In copper deficiency, brainstem and lumbar involvement can also be seen, with spinal cord atrophy in severe cases. In vitamin E deficiency, the T2 signal hyperintensities are seen in the posterior columns as well as cerebellar atrophy. Intrathecal chemotherapy-associated myelopathy (i.e., methotrexate, cytarabine), T2 hyperintensities in the dorsal columns will also be seen. Arachnoiditis due to intrathecal chemotherapy may show enhancement of the lumbosacral nerve roots, presenting clinically as lumbosacral radiculopathy.^9-10

In hepatic myelopathy, there is an increased pallidal signal on the T1 cranial MRI and, rarely, also, increased cervical cord signal on the T2 images. Symmetric demyelination of the lateral corticospinal tracts, posterior columns, and spinocerebellar tracts may be seen.

Although there is low incidence, in ketoacidosis myelopathy, MRI can demonstrate T2 hyperintensities associated with cord edema. In the case of spinal cord infarction occurring as a complication of diabetic ketoacidosis, the lesions may present as hyperintense signals on T2-weighted imaging with restricted diffusion in the affected area(s).¹¹

Heroin myelopathy can show selective involvement of the lateral and posterior columns on T2, with evidence of cord swelling with gadolinium enhancement resembling transverse myelitis. Conversely, MR imaging in acute heroin myelopathy may be normal. MRI can also be normal with radiation myelopathy. Over time, MR imaging may reveal spinal cord swelling with T2 hypersensitivity and variable gadolinium enhancement.

In radiation myelopathy, the imaging will show spinal cord changes in the same area as bone marrow changes from radiation exposure. T1 hyperintensity of the vertebral bodies at the site of radiation exposure is commonly seen. In delayed radiation myelopathy, MRI demonstrates cord edema and longitudinally extensive T2 hyperintensity and T1 hypointensity. Spinal cord involvement by tumor needs to be ruled out prior to attributing the myelopathy to radiation.

The advent of immunotherapy, particularly immune checkpoint inhibitors (ICIs), has transformed cancer treatment paradigms. However, these revolutionary therapies carry a risk of immune-related adverse events (irAEs), including rare but potentially devastating neurological complications. Among these, ICI-induced transverse myelitis represents a particularly severe neurological irAE that requires prompt recognition. MR imaging commonly demonstrates extensive T2 hyperintensities of the spinal cord as is seen in subacute combined degeneration.¹²

Fluorosis may demonstrate generalized osteosclerosis with osteophytes throughout the spine and ligamentous calcification, as well as calcification of the interosseous membrane of the forearm on x-ray.

Supplemental assessment tools

Additional testing is done as indicated by neurologic impairment, including urodynamics for neurogenic bladder dysfunction and spirometry for respiratory dysfunction. If examination demonstrates unequivocal evidence of a spinal cord process and the MRI is normal, consider and test for degenerative, infectious and metabolic causes of myelopathy including EMG.¹³ In the case of EMG, studies of vitamin B12, copper, and vitamin E deficiency myelopathy have demonstrated patterns of predominantly axonal peripheral neuropathy with somatosensory evoked potential showing slowing of central somatosensory pathways.

Early predictions of outcomes

Because of the diverse nature of these conditions, prognostication is difficult. Generally, the more rapid the onset and more severe the neurologic deficits, the poorer the prognosis is for complete recovery. Extent of MRI involvement in vitamin B12 deficiency has not been shown to correlate with degree of recovery.

Environmental

In addition to the usual assessment of environment that is appropriate for persons with functional deficits as a result of spinal cord injury, these conditions are often characterized by loss of proprioception. Thus, environmental assessment should include focus on reducing fall risk, including lights for nighttime, grab bars in the bath (where eyes must be closed and impaired proprioception becomes more noticeable), among others.

Rehabilitation Management and Treatments

Available or current treatment guidelines

Specific interventions to address the underlying cause depend on the specific etiology, and include the following²

• Vitamin B12 deficiency: intramuscular vitamin B12 1000 µg daily for 14 days, then monthly thereafter.
• Folate deficiency: oral folate 1 mg 3 times a day until hematologic values normalize, followed by 1 mg daily as maintenance. Increase dietary intake of green, leafy vegetables and citrus fruits.
• Copper deficiency: oral copper 8 mg daily for 1 week, then 6 mg daily for 1 week, then 4 mg daily for 1 week, then 2 mg daily. Discontinue intake of exogenous zinc in patients with excess zinc as a cause.
• Vitamin E deficiency: vitamin E 200 to 1000 mg daily (may be oral or intramuscular).
• Hepatic myelopathy: possible benefit of early liver transplantation. If hepatic myelopathy occurs after transjugular intrahepatic portosystemic shunt (TIPS), endovascular occlusion of the TIPS has been shown to be clinically effective.
• Nitrous oxide toxicity: cessation of chronic exposure. Give intramuscular vitamin B12 with acute nitrous oxide poisoning. There may be a role for methionine supplementation. Consider prophylactic vitamin B12 prior to surgery in individuals with a borderline vitamin B12, if expected to get nitrous oxide anesthesia.
• Intrathecal-chemotherapy toxicity: Cessation of intrathecal chemotherapy. Dextromethorphan has been shown to improve methotrexate-associated neurotoxicity in the brain but mixed results have been reported for myelopathy (9). Administration of folate metabolites led to resolution of symptoms in one case.¹⁴
• Treatment for ICI-induced transverse myelitis is based on symptom severity and can range from supportive care, holding ICI, permanently discontinuing ICI, corticosteroids, IVIG, and plasmapheresis.¹⁵
• Radiation toxicity: corticosteroids are the most common first treatment. Other strategies have ben examined with limited clinical data to support their use, including bevacizumab and hyperbaric oxygen.¹⁶ The radiation dose to limit the risk of radiation myelopathy is 45-50 Gy, delivered in 1.8-2.0 Gy per fraction, administered over 4-5 weeks (22-25 fractions).
• Cassava toxicity: “wetting method” involving mixing cassava with flour and letting it sit has greatly reduced incidence in areas of Africa.
• Lathyrism: preventable by mixing grass pea with cereals, or detoxification through aqueous leaching.
• Organophosphate toxicity: pralidoxime and atropine for acute toxicity. Prevention by use of gloves and protective clothing.
• Fluorosis: surgery may be required for evidence of cord compression.

In addition to these specific treatments, rehabilitative strategies should focus on addressing the associated impairments. This will include therapy for transfers, strengthening, gait training with a device as needed, and evaluation of ADLs needs with provision of appropriate equipment. Patients with proprioceptive deficits will need to be trained in accommodative techniques, such as the use of visual feedback, to compensate for loss of joint position sense.

Patient & family education

For conditions caused by toxins, especially as a result of dietary exposure, education will be key to preventing future exposure. Many of the nutrient deficiencies require lifelong supplementation, and patient education regarding this will be key.

Emerging/unique interventions

Similar to other nontraumatic myelopathies.

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

These conditions should be in the differential diagnosis of unexplained weakness, sensory impairment, or gait disturbance, because they are uncommon yet often treatable.

Cutting Edge/Emerging and Unique Concepts and Practice

Bevacizumab has been shown to be effective in treating radiation necrosis of the brain and might be a new avenue for treatment of progressive radiation-induced myelopathy.^17,18

Use of Immunotherapy like plasmapheresis or high dose IV steroids have been reported for myelopathies of acute presentation however outcomes range from no improvement to significant improvement.⁶

Use of neuroprotective agents like amifostine and antioxidants (such as N-acetylcysteine) have shown promise in decreasing effects of radiation myelopathy. Mitochondrial protectants (like coenzyme Q10) may also be protective by mitigating oxidative stress, although evidence for radiation induced myelopathy is currently limited.^19,20  

Gaps in the Evidence-Based Knowledge

It is possible that other myelopathies may also be the result of impaired vitamin B12 metabolism, though the precise role may not be fully defined. For example, the vacuolar myelopathy associated with acquired immunodeficiency syndrome is thought to possibly be because of a metabolic disorder of the vitamin B12-dependent transmethylation pathway, induced by the human immunodeficiency virus or cytokine activation.

Further study into the mechanism and treatment of heroin myelopathy is needed. Several proposed mechanisms exist including the immune-mediated response previously mentioned as well as a direct toxic effect of heroin on the CNS and vasculitis.

Clioquinol was used as a topical and intestinal antiseptic and to treat acrodermatitis enteropathica until it was banned after epidemiological studies identified it as the cause of subacute myelo-opticoneuropathy in 1970. It acts as a zinc chelator in the intestine and causes an increase in systemic zinc absorption.  Therefore, it is hypothesized that copper deficiency may have been the cause of this disorder.

Other treatments, in addition to vitamin supplementation, need to be researched to establish effective treatments especially for chemotherapy induced myelopathy.

With the increasing roles of repeated irradiation and stereotactic radiation, there needs to be continued studies on the volume of radiation that can affect the spinal cord.

References

1. -“lkjm bnAsakly, S., Magen-Rimon, R., Ighbariya, A., Marjih-Shallufi, M., Ben-Porat, T., Ravid, S., … & Weiss, R. (2021). Bariatric surgery-associated myelopathy. Obesity Facts, 14(4), 431-439.
2. Bünül, S. D., Sarıkaya, C. E., Öztürk, O., & Sarıkaya, C. (2021). A brief case series of radiation associated myelopathy. Neurosciences Journal, 26(4), 392-395.
3. Huang, J., et al. (2024). “Long-term outcomes and predictive factors of radiation myelopathy after spinal cord radiation.” Clinical Cancer Research, 30(1), 12-21.
4. Zhao, L., et al. (2021). “Radiation-induced myelopathy: New insights and advances in diagnosis and treatment.” Journal of Neuro-Oncology, 155(2), 367-375.
5. Pardo, C. A. (2024). Clinical approach to myelopathy diagnosis. CONTINUUM: Lifelong Learning in Neurology, 30(1), 14-52.
6. Holroyd, K. B., & Berkowitz, A. L. (2024). Metabolic and toxic myelopathies. CONTINUUM: Lifelong Learning in Neurology, 30(1), 199-223.
7. Fink, J. K. (2008). Hereditary myelopathies. CONTINUUM: Lifelong Learning in Neurology, 14(3), 58-70.
8. Agarwal, V., Shah, L. M., Parsons, M. S., Boulter, D. J., Cassidy, R. C., Hutchins, T. A., … & Corey, A. S. (2021). ACR appropriateness criteria® myelopathy: 2021 update. Journal of the American College of Radiology, 18(5), S73-S82.
9. Cachia, D., Kamiya-Matsuoka, C., Pinnix, C. C., Chi, L., Kantarjian, H. M., Cortes, J. E., … & Woodman, K. (2015). Myelopathy following intrathecal chemotherapy in adults: a single institution experience. Journal of neuro-oncology, 122, 391-398.
10. Counsel, P., & Khangure, M. (2007). Myelopathy due to intrathecal chemotherapy: magnetic resonance imaging findings. Clinical radiology, 62(2), 172-176.
11. Dixon, A. N., Jude, E. B., Banerjee, A. K., & Bain, S. C. (2006). Simultaneous pulmonary and cerebral oedema, and multiple CNS infarctions as complications of diabetic ketoacidosis: a case report. Diabetic medicine, 23(5), 571-573.
12. Picca, A., Berzero, G., Bihan, K., Jachiet, V., Januel, E., Coustans, M., … & Psimaras, D. (2021). Longitudinally extensive myelitis associated with immune checkpoint inhibitors. Neurology: Neuroimmunology & Neuroinflammation, 8(3), e967.
13. Schmalstieg, W. F., & Weinshenker, B. G. (2010). Approach to acute or subacute myelopathy. Neurology, 75(18_supplement_1), S2-S8.
14. Ackermann, R., Semmler, A., Maurer, G. D., Hattingen, E., Fornoff, F., Steinbach, J. P., & Linnebank, M. (2010). Methotrexate-induced myelopathy responsive to substitution of multiple folate metabolites. Journal of neuro-oncology, 97, 425-427.
15. Schneider, B. J., Naidoo, J., Santomasso, B. D., Lacchetti, C., Adkins, S., Anadkat, M., … & Bollin, K. (2021). Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update. Journal of Clinical Oncology, 39(36), 4073-4126.
16. Wong, C. S., Fehlings, M. G., & Sahgal, A. (2015). Pathobiology of radiation myelopathy and strategies to mitigate injury. Spinal Cord, 53(8), 574-580.
17. Levin, V. A., Bidaut, L., Hou, P., Kumar, A. J., Wefel, J. S., Bekele, B. N., … & Jackson, E. F. (2011). Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. International Journal of Radiation Oncology* Biology* Physics, 79(5), 1487-1495.
18. Chamberlain, M. C., Eaton, K. D., & Fink, J. (2011). Radiation-induced myelopathy: treatment with bevacizumab. Archives of neurology, 68(12), 1608-1609.
19. Kim, W. D., & Park, W. Y. (2006). The effect of pentoxifylline on radiobiological parameters in the rat radiation myelopathy. Cancer Research and Treatment: Official Journal of Korean Cancer Association, 38(4), 229-233.
20. Mohamed, H. A., & Said, R. S. (2021). Coenzyme Q10 attenuates inflammation and fibrosis implicated in radiation enteropathy through suppression of NF-kB/TGF-β/MMP-9 pathways. International Immunopharmacology, 92, 107347.

Original Version of the Topic 

Susan V. Garstang, MD. Metabolic / Nutritional / Toxic / Radiation myelopathies. 9/20/2013.

Previous Revision(s) of the Topic 

Thomas Kiser, MD and Noel Brown, MD. Metabolic / Nutritional / Toxic / Radiation myelopathies. 3/24/2017

Sol Abreu-Sosa, MD, Alethea Appavu, DO, Ishita Jain, MD. Metabolic / Nutritional / Toxic / Radiation Myelopathies. 12/22/2021

Author Disclosure

Sol Abreu-Sosa, MD
Nothing to Disclose

Obada Obaisi, MD, FAAPMR, DipABLM
Nothing to Disclose

Roi Medina, DO
Nothing to Disclose

Lena Mishack, MD
Nothing to Disclose