Subacute combined degeneration of spinal cord, also known as myelosis funiculus, or funicular myelosis, also Lichtheim's disease, and Putnam-Dana syndrome, refers to degeneration of the posterior and

lateral column The lateral grey column (lateral column, lateral cornu, lateral horn of spinal cord, intermediolateral column) is one of the three grey columns of the spinal cord (which give the shape of a butterfly); the others being the anterior and posterio ...

s of the

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spi ...

as a result of vitamin B₁₂ deficiency (most common),

vitamin E deficiency Vitamin E deficiency in humans is a very rare condition, occurring as a consequence of abnormalities in dietary fat absorption or metabolism rather than from a diet low in vitamin E. Collectively the EARs, RDAs, AIs and ULs for vitamin E and other ...

, and

copper deficiency Copper deficiency, or hypocupremia, is defined either as insufficient copper to meet the needs of the body, or as a serum copper level below the normal range. Symptoms may include fatigue, decreased red blood cells, early greying of the hair, a ...

. It is usually associated with

pernicious anemia Pernicious anemia is a type of vitamin B12 deficiency anemia, a disease in which not enough red blood cells are produced due to the malabsorption of vitamin B12. Malabsorption in pernicious anemia results from the lack or loss of intrinsic fa ...

Signs and symptoms

The onset is gradual and uniform. The pathological findings of subacute combined degeneration consist of patchy losses of

myelin Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be ...

in the dorsal and lateral columns. Patients present with weakness of the legs, arms, and trunk, and tingling and numbness that progressively worsens. Vision changes and change of mental state may also be present. Bilateral spastic

paresis In medicine, paresis () is a condition typified by a weakness of voluntary movement, or by partial loss of voluntary movement or by impaired movement. When used without qualifiers, it usually refers to the limbs, but it can also be used to desc ...

may develop and pressure, vibration and touch sense are diminished. A positive

Babinski sign The plantar reflex is a reflex elicited when the sole of the foot is stimulated with a blunt instrument. The reflex can take one of two forms. In healthy adults, the plantar reflex causes a downward response of the hallux (flexion). An upward re ...

may be seen. Prolonged deficiency of vitamin B₁₂ leads to irreversible nervous system damage. HIV-associated vacuolar myelopathy can present with a similar pattern of dorsal column and

corticospinal tract The corticospinal tract is a white matter motor pathway starting at the cerebral cortex that terminates on lower motor neurons and interneurons in the spinal cord, controlling movements of the limbs and trunk. There are more than one million neur ...

demyelination A demyelinating disease is any disease of the nervous system in which the myelin sheath of neurons is damaged. This damage impairs the conduction of signals in the affected nerves. In turn, the reduction in conduction ability causes deficiency i ...

. It has been thought that if someone is deficient in vitamin B₁₂ and

folic acid Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...

, the vitamin B₁₂ deficiency must be treated first. However, the basis for this has been challenged, although due to ethical considerations it is no longer able to be tested if "neuropathy is made more severe as a result of giving folic acid to vitamin B₁₂- deficient individuals". And that if this were the case, then the mechanism remains unclear. Administration of

nitrous oxide Nitrous oxide (dinitrogen oxide or dinitrogen monoxide), commonly known as laughing gas, nitrous, or nos, is a chemical compound, an oxide of nitrogen with the formula . At room temperature, it is a colourless non-flammable gas, and has a ...

anesthesia can precipitate subacute combined degeneration in people with subclinical vitamin B₁₂ deficiency, while chronic nitrous oxide exposure can cause it even in persons with normal B₁₂ levels. Posterior column dysfunction decreases vibratory sensation and

proprioception Proprioception ( ), also referred to as kinaesthesia (or kinesthesia), is the sense of self-movement, force, and body position. It is sometimes described as the "sixth sense". Proprioception is mediated by proprioceptors, mechanosensory neurons ...

(joint sense). Lateral corticospinal tract dysfunction produces

spasticity Spasticity () is a feature of altered skeletal muscle performance with a combination of paralysis, increased tendon reflex activity, and hypertonia. It is also colloquially referred to as an unusual "tightness", stiffness, or "pull" of muscles. ...

and dorsal

spinocerebellar tract The spinocerebellar tract is a nerve tract originating in the spinal cord and terminating in the same side (ipsilateral) of the cerebellum. Origins of proprioceptive information Proprioceptive information is obtained by Golgi tendon organs and mu ...

dysfunction causes

ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...

Cause

In general, the most common cause of this condition is a deficiency of vitamin B₁₂. This may be due to a dietary deficiency, malabsorption in the

terminal ileum The ileum () is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine ma ...

, lack of

intrinsic factor Intrinsic factor (IF), cobalamin binding intrinsic factor, also known as gastric intrinsic factor (GIF), is a glycoprotein produced by the parietal cells (in humans) or chief cells (in rodents) of the stomach. It is necessary for the absorption o ...

secreted from gastric parietal cells, or low gastric pH inhibiting attachment of intrinsic factor to ileal receptors.

Vitamin E deficiency Vitamin E deficiency in humans is a very rare condition, occurring as a consequence of abnormalities in dietary fat absorption or metabolism rather than from a diet low in vitamin E. Collectively the EARs, RDAs, AIs and ULs for vitamin E and other ...

, which is associated with malabsorption disorders such as

cystic fibrosis Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. O ...

and

Bassen-Kornzweig syndrome Abetalipoproteinemia (also known as: Bassen-Kornzweig syndrome, microsomal triglyceride transfer protein deficiency disease, MTP deficiency, and betalipoprotein deficiency syndrome) is a disorder that interferes with the normal absorption of fat ...

, can cause a similar presentation due to the degeneration of the

dorsal column Dorsal (from Latin ''dorsum'' ‘back’) may refer to: * Dorsal (anatomy), an anatomical term of location referring to the back or upper side of an organism or parts of an organism * Dorsal, positioned on top of an aircraft's fuselage * Dorsal co ...

Diagnosis

Serum vitamin B₁₂,

methylmalonic acid Methylmalonic acid (MMA) (conjugate base methylmalonate) is a dicarboxylic acid that is a ''C''-methylated derivative of malonate. The coenzyme A linked form of methylmalonic acid, methylmalonyl-CoA, is converted into succinyl-CoA by methylmalonyl ...

Schilling test The Schilling test was a medical investigation used for patients with vitamin B (cobalamin) deficiency. The purpose of the test was to determine how well a patient is able to absorb B12 from their intestinal tract. The test is now considered obs ...

, and a complete blood count, looking for

megaloblastic anemia Megaloblastic anemia is a type of macrocytic anemia. An anemia is a red blood cell defect that can lead to an undersupply of oxygen. Megaloblastic anemia results from inhibition of DNA replication, DNA synthesis during red blood cell production. ...

if there is also

folic acid deficiency Folate deficiency, also known as vitamin B9 deficiency, is a low level of folate and derivatives in the body. Signs of folate deficiency are often subtle. A low number of red blood cells (anemia) is a late finding in folate deficiency and folate ...

macrocytic anemia The term ''macrocytic'' is from Greek words meaning "large cell". A macrocytic class of anemia is an ''anemia'' (defined as blood with an insufficient concentration of hemoglobin) in which the red blood cells (erythrocytes) are larger than their ...

. The Schilling test is no longer available in most areas. MRI-T2 images may reveal increased signal within the white matter of the spinal cord, predominantly in the posterior columns and possibly in the spinothalamic tracts.

Treatment

Therapy with vitamin B₁₂ results in partial to full recovery where SACD has been caused by vitamin B₁₂ deficiency, depending on the duration and extent of

neurodegeneration A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...

References

External links

{{Spinal cord lesions Histopathology Neurodegenerative disorders