Metabolic Conditions Affecting the Spinal Cord


Metabolic disorders of the spinal cord are less common than metabolic disorders of the brain and peripheral nerves. Such metabolic myelopathies can be secondary to nutritional deficiencies, especially vitamin B 12 deficiency, or to systemic metabolic disorders.

VITAMIN B 12 DEFICIENCY

Subacute combined degeneration (SCD) of the spinal cord is a symmetric spongy vacuolation and degeneration of myelin that results from deficiency of vitamin B 12 . It affects the dorsal and lateral columns of the cervicothoracic spinal cord symmetrically, leading to symmetric paresthesias, stiffness, and gait unsteadiness and is worse in the lower than the upper extremities.

Epidemiology

The prevalence of vitamin B 12 deficiency is estimated at 4.8% to 12% in the elderly population living in the community and up to 30% to 40% among hospitalized elderly people. SCD is most commonly diagnosed between the fifth and eighth decades of life. Subclinical myelopathy occurs in up to 40% of patients with pernicious anemia. About one fourth of the patients with SCD have no known hematologic abnormalities.

Dietary deficiency of vitamin B 12 may result from insufficient ingestion of vitamin B 12 in strict vegetarians (vegans). Malabsorption of ingested vitamin B 12 may occur in patients with insufficient production of intrinsic factor (pernicious anemia); hypochlorhydria (partial/complete gastrectomy); insufficient absorption of vitamin B 12 (ileal resection, multiple causes of intestinal malabsorption including celiac disease, chronic pancreatic insufficiency, Crohn's disease); or intestinal competition for the ingested vitamin B 12 (bacterial overgrowth in blind-loop syndrome, infestation with the fish tapeworm Diphyllobothrium latum ). SCD of the spinal cord can be also caused by nitrous oxide abuse, copper deficiency, folate deficiency, human immunodeficiency virus (HIV) infection, and rare inherited defects of methylation.

Clinical Presentation

Vitamin B 12 deficiency causes megaloblastic anemia, glossitis, gastrointestinal disturbances, SCD of the spinal cord, and peripheral neuropathy. The clinical presentation of SCD reflects (1) dysfunction of the dorsal columns (disturbed vibration sense, disturbed position sense, and ataxia), (2) dysfunction of the lateral corticospinal tracts (hyperreflexia, spasticity, and extensor plantar responses), and (3) dysfunction of the spinothalamic tracts (sensory loss). Early symptoms of SCD consist of symmetric paresthesias, which are first distal, then also proximal; stiffness; and gait unsteadiness. Progression leads to spastic paraparesis, ataxia, and anesthesia of the lower limbs and trunk. The upper extremities are typically less affected.

The diagnosis of vitamin B 12 deficiency is confirmed by demonstrating low serum levels of vitamin B 12 or, if the vitamin B 12 level is borderline, elevated levels of homocysteine and methylmalonic acid. Hematologic changes are not reliable markers for vitamin B 12 deficiency. Pernicious anemia is confirmed by the Schilling test or by the presence of anti–intrinsic factor antibodies. The treatment of vitamin B 12 deficiency consists of monthly intramuscular injections of vitamin B 12 . After supplementation with vitamin B 12 , patients may show clinical and radiologic improvement. Reversal of symptoms, however, is inversely proportional to symptom duration and severity.

Pathophysiology

SCD of the spinal cord is thought to result from defective methylation of myelin basic protein and other central nervous system proteins. Both vitamin B 12 and folate are important coenzymes in the production of methionine, which acts as a methyl-group donor in the synthesis of myelin basic protein.

Vitamin B 12 is mostly found in animal food (meat, dairy products, and yeasts). It is released during gastric digestion and must bind to intrinsic factor, a glycoprotein produced by the gastric parietal cells, in order to be absorbed in the distal ileum and stored in the liver. Pernicious anemia is an immune-mediated process that destroys the gastric parietal cells, so less intrinsic factor is available. Conditions such as gastric surgery or gastric reconstruction, intestinal bacterial overgrowth, and gastric atrophy (possibly secondary to Helicobacter pylori infection) cause hypochlorhydria and inability to release vitamin B 12 from food. Other causes of malabsorption of vitamin B 12 are surgical resection of the terminal ileum and a variety of disorders that result in damage to the last 80 cm of the small bowel mucosa (e.g., Crohn's disease, lymphoma, tuberculosis, Whipple's disease, and celiac disease).

Pathology

In chronic SCD, the spinal cord may appear atrophic with discoloration of the posterior and lateral columns, especially in the lower cervical and thoracic regions.

Early findings of SCD include spongy vacuolation and degeneration of myelin, most commonly in the thoracic region. Initially, there is symmetric involvement of the posterior columns (fasciculi gracilis and cuneatus) and later the lateral columns (corticospinal and spinocerebellar tracts) ( Fig. 17-1 ). Perivascular demyelination and inflammation may cause breakdown of the blood-brain barrier. Chronically, astrocytic gliosis, axonal degeneration, and macrophage infiltration of the posterior spinal cord are observed. In severe cases the anterior columns are also involved. Extension to the medulla has been reported.

FIGURE 17-1, Vitamin B 12 deficiency. Degeneration of the myelin of the posterior and lateral columns.

Imaging

CT

CT of the spine is often normal. Mild cord swelling can be seen in some cases.

MRI

T2-weighted (T2W) images demonstrate increased signal intensity of the dorsal and possibly lateral columns of the spinal cord ( Fig. 17-2 ). There may be mild contrast enhancement, or not. Axial MR images display the symmetric involvement of the dorsal (and/or lateral) columns as increased T2 signal in an “inverted V” or “inverted rabbit ears” configuration. Sagittal sequences show continuous lengths of increased T2 signal running vertically for long distances along the dorsal surface of the thoracic or cervicothoracic cords. This is a helpful sign. In SCD a continuous area of abnormal signal extends over several vertebral bodies, whereas in multiple sclerosis and other demyelinating disorders the cord lesions are often multiple not single and each segment is typically shorter than two vertebral bodies. The lateral columns may not show signal abnormalities, even when there is clinical evidence they are affected.

FIGURE 17-2, Vitamin B 12 deficiency. Axial T2W MR image of the cervical spine demonstrates abnormal symmetric increased signal in the posterior ( arrow ) and lateral columns ( arrowhead ) of the cervical spinal cord.

On follow-up MRI, the T2 signal abnormalities of the posterior columns may appear decreased when vitamin B 12 treatment is initiated promptly.

NITROUS OXIDE TOXICITY

Nitrous oxide toxicity is a myelopathy that develops in patients with clinically silent or borderline vitamin B 12 toxicity, who are then exposed to nitrous oxide anesthesia.

Epidemiology

Nitrous oxide is an inhaled gas used as an anesthetic in dentistry and as a propellant in the food industry (e.g., in whipped cream dispensers). Myelopathy may develop 2 to 6 weeks after nitrous oxide anesthesia. Most patients are found to have a subclinical or undiagnosed vitamin B 12 deficiency. Several cases of nitrous oxide neurotoxicity have been described after abuse of nitrous oxide by health care providers or occupational exposure, even in subjects with normal vitamin B 12 levels.

Clinical Presentation

The signs and symptoms of toxic nitrous oxide myelopathy are analogous to those seen in SCD of the spinal cord secondary to vitamin B 12 deficiency. Signs of involvement of the posterior columns include loss of position and vibration sense, ataxia, and broad-based gait. Dysfunction of the corticospinal tracts may manifest as weakness, spasticity, hyperreflexia, clonus, incontinence, and extensor plantar response. There may also be mental status changes, emotional instability, and, in some cases, psychosis with intellectual deterioration.

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