1	METABOLIC CONDITIONS AFFECTING THE SPINAL CORD
2	DISCLOSURES M. Vittoria Spampinato: no disclosures Amit K. Agarwal: no disclosures Zoran Rumboldt: Bracco Diagnostics (consultant)
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4	ANATOMY WHITE MATTER TRACTS OF THE SPINAL CORD
5	MRI PROTOCOL SPINAL CORD
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7	VITAMIN B12 DEFICIENCY SUBACUTE COMBINED DEGENERATION Myelopathy secondary to vitamin B12 deficiency It may result from insufficient ingestion or impaired absorption of vitamin B12 High prevalence among the elderly (4.8 -12% in the community; 30 - 40% among hospitalized elderly people) Pernicious anemia is a common cause of vitamin B12 malabsorption in the United States Other etiologies: partial or complete gastrectomy, ileal resection, fish tapeworm infestation, strict vegan diet
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17	COPPER DEFICIENCY MYELOPATHY Acquired myeloneuropathy in patients with copper deficiency Rare in humans due to the ubiquitous availability of copper and its low daily requirement Parenteral or enteral feeding without copper supplementation, nephrotic syndrome, gastrectomy, malabsorption, premature and malnourished infants Ingestion of copper-chelating agents, complication of penicillamine therapy, or secondary to excessive zinc ingestion Menkes disease: X-linked inherited disorder of copper metabolism characterized by deficit of copper absorption and transport, which develops in infancy
18	COPPER DEFICIENCY MYELOPATHY Clinical presentation Ataxic gait, loss of proprioception and vibration in the distal lower limbs, and loss of perception of pinprick and touch in a stocking distribution Abnormal findings of the upper limbs are usually subtle or absent Hematologic findings: anemia, neutropenia, sideroblastosis, and myelodysplastic syndrome Serum copper and ceruloplasmin levels are usually markedly decreased Treatment with oral copper supplementation (2 mg/die) typically prevents further neurological deterioration and in some cases leads to clinical improvement
19	COPPER DEFICIENCY MYELOPATHY MRI Findings High T2 signal in the spinal cord involving the dorsal columns and the central spinal cord; exclusive involvement of the central spinal cord has been described Mild spinal cord atrophy No spinal cord contrast enhancement has been reported in copper deficiency myelopathy Following increase in serum copper levels, the signal abnormalities in the dorsal columns may improve
20	COPPER DEFICIENCY MYELOPATHY
21	COPPER DEFICIENCY MYELOPATHY
22	NITROUS OXIDE TOXICITY Nitrous oxide is an inhaled anesthetic used in dentistry and a propellant used in the food industry (e.g., in whipped cream dispensers) Myelopathy can occur in patients exposed to nitrous oxide anesthesia with clinically silent or borderline vitamin B12 toxicity Development of myelopathy 2-6 weeks after nitrous oxide anesthesia in subjects with subclinical or undiagnosed vitamin B12 deficiency Nitrous oxide neurotoxicity after abuse by health care providers and after occupational exposure have been described even in subjects with normal vitamin B12 levels
23	NITROUS OXIDE TOXICITY Clinical presentation Signs and symptoms analogous to those seen in SCD of the spinal cord secondary to vitamin B12 Signs of involvement of the posterior columns (e.g., loss of position and vibration senses, ataxia, broad-based gait) and of the corticospinal tracts (e.g., weakness, spasticity, hyperreflexia, clonus, incontinence, extensor plantar response) MRI Findings MRI findings are similar to those seen in SCD of the spinal cord secondary to vitamin B12 deficiency Symmetric T2 hyperintensities of the posterior columns and/or lateral columns, possible posterior columns enhancement after gadolinium administration
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25	MYELOPATHY IN SYSTEMIC METABOLIC DISORDERS Spinal cord involvement in diabetes mellitus and chronic liver disease The prevalence of diabetic myelopathy is currently unknown. Research studies on diabetes complications have focused mainly on the peripheral nervous system, although involvement of the central nervous system and in particular of the spinal cord has been previously described. Progressive myelopathy is an uncommon complication of chronic liver disease with portal hypertension, observed less frequently than hepatic encephalopathy and the two conditions can coexist.
26	MYELOPATHY IN SYSTEMIC METABOLIC DISORDERS Clinical Presentation Diabetic myelopathy: leg weakness, abnormal gait, sensory peripheral neuropathies, abnormal sense of joint position lower extremities, ataxia, and brisk deep tendon reflexes Hepatic myelopathy: walking difficulties, tremor, increased muscle tone, spastic paraparesis, brisk deep tendon reflexes and extensor plantar responses, in absence of significant sensorial involvement or sphincterial disturbances
27	MYELOPATHY IN SYSTEMIC METABOLIC DISORDERS MRI Findings The imaging features of hepatic and diabetic myelopathy have not been systematically evaluated MRI of the spinal cord was normal or showed mild atrophy in the few cases of hepatic myelopathy reported in the literature Spinal cord atrophy occurs in patients with diabetes mellitus and diabetic peripheral neuropathy even in absence of clinical signs of myelopathy. Despite spinal cord abnormalities are present in up to 41% of autopsies in diabetic patients, few cases of diabetic myelopathy documented with MRI are reported in the literature
28	MYELOPATHY IN SYSTEMIC METABOLIC DISORDERS
29	HIV-related Vacuolar Myelopathy Mimics vitamin B12 deficiency SCD Posterior (arrowheads) and lateral column involvement Signal abnormalities extending over multiple segments Middle and lower thoracic spine Clinical picture: paraparesis, LE sensory abnormalites, and neurogenic bladder, evolving over weeks or months
30	DIFFERENTIAL DIAGNOSIS OF MYELOPATHY Neoplasms Demyelinating diseases SCD secondary to vitamin B12 deficiency, copper deficiency, nitrous oxide toxicity Infectious etiologies: HIV, tabe dorsalis, HTLV-1, HSV, CMV, EBV, enteroviruses Inflammatory conditions (e.g., sarcoidosis) Paraneoplastic syndrome Idiopathic transverse myelitis Collagen vascular diseases Post-RT myelopathy AVM and dural AVF Spinal cord infarct
31	KEY POINTS Symmetric signal abnormalities confined to the posterior columns + / - lateral columns over multiple vertebral segments suggests a metabolic etiology of the myelopathy Myelopathy secondary to vitamin B12 deficiency, nitrous oxide toxicity, copper deficiency, HIV vacuolar myelopathy, and tabes dorsalis all have similar imaging appearance Serum levels of vitamin B12, homocysteine, methylmalonic acid, copper, ceruloplasmin, urine-24 h copper excretion, Lyme disease, syphilis, HIV and HSV serologic tests should be part of the work up of patients with myelopathy of undetermined origin
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