Friday, November 15, 2024

Subacute combined Degeneration of the Spinal Cord

 

 Subacute Combined Degeneration of the Spinal Cord.

 P.K Ghatak, MD

This name Subacute Combined Degeneration of the Spinal Cord simply indicates how fast a disease develops and where the pathological changes happen in the spinal cord. The name does not give any hint of a cause or symptom it produces.

Subacute Combined Degeneration of the Spinal Cord (SCD of the SC) is a slowly developing disease due to degeneration of the myelin of the spinal cord. The spinal cord, like a cable line, containing several bundles, each bundle carries electrical signals either to or from the brain. Each bundle carries a separate set of information. A cross-section of the spinal cord at the neck level is shown here.




In SCD the Dorsal and Lateral columns of the upper thoracic and lower cervical part of the spinal cord are affected and in late cases, the descending fibers of the motor cortex, the Corticospinal tract, of the upper cervical region are damaged.

The dorsal column carries fine touch, vibratory sensation, conscious sensation of position of the body (proprioception), two point discrimination from the skin and joints to the sensory area of the brain.

The lateral column carries pain and temperature sensations from the skin to the brain.

The corticospinal tract carries voluntary motor impulses from the brain to the lower motor neurons located in the Ventral Horn of the spinal cord.

The cause of SCD of the SP:

It is due to a deficiency of vitamin B12.

Vitamin B12 is a cofactor of two important enzymes, (a) Methionine synthase and (b) Methymelonyl CoA mutase.

Methionine synthase is required for methionine synthesis, a crucial amino acid required for myelin synthesis.

Methymelonyl CoA mutase is required for fatty acid synthesis, an important ingredient for myelin. This enzyme is also important for the synthesis of Thymidine which goes to from DNA in humans, Macrocytic anemia develops due to a deficiency of this enzyme.

In the absence of B12 the myelin breaks down and is not repaired due to a deficit of two critical components of myelin and as a result the symptoms of SCD of SC develop.

Blood levels of vitamin B12 do not correspond with the tissue levels, which show a deficit much earlier than B12 levels in the blood due to the fact that most B12 in the blood is combined with protein.


Symptoms of SCD:

The initial symptoms are tingling and numbness of the legs, symmetrical in distribution on each side of the body and the deficit areas gradually extend upwards. This is followed by loss of position sensation, difficulty in coordination and ambulation. Later, loss of temperature sensation in the lower and upper extremities results in thermal burns. As the disease further advances, clumsiness of movements, and muscle weakness, spasticity of limbs and paraplegia develop due to corticospinal tract involvement.

Causes of B12 deficiency:

Vitamin B12 is a water soluble vitamin. Animal protein, eggs, fish, shellfish and milk are the only sources. The highest concentration is seen in abalone and animal liver. Plants are no vitamin. In the USA, the cereals are fortified with B12.

Vitamin B12 deficiency develops for the following reasons.

  1. Diet.

  2.  Parietal cell disease of the stomach.

  3. Disease of the terminal ileum. 

  4. Congenital.

  5.   Medications

Diet.

The vegans in the USA are at risk of developing B12 deficiency, pregnancy and breastfeeding are risk factors.

Parietal cells.

Chronic gastritis destroys the parietal cells of the stomach. The intrinsic factor is a glycoprotein. It combines with vitamin B12 released from the food, and the composite is protected from further digestion and is carried to the terminal ileum for absorption. Partial gastrectomy, Roux-en-Y operation, bariatric surgery, etc. remove the parietal cell population and B12 deficiency occurs.

Autoimmune disease.

Antibodies produced in the body to fight pathogens, but in this case, the antibodies mistakenly think that parietal cells as foreign and attack and destroy them, in other cases, the antibodies attack the intrinsic factor itself and eliminate it from the body. The final outcome is vitamin B12 absorption stops. Three diseases result from vitamin B12 deficiency.  One is pernicious anemia, two-  peripheral neuropathy and three - SCD of the SC.


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Diseases of ileum.

Crohn's disease, malabsorption syndrome, short loop syndrome, ulcerative colitis, sprue, lymphoma of the abdomen and amyloidosis are some of the diseases producing B12 deficiency.

Fish tapeworm – A parasitic tapeworm, Dibothriocephalus latus, steals vitamin B12. Humans acquire this parasite by eating raw fish. Until now, this fish tapeworm infestation was confined to the Far East but the popularity of sushi food in the West putting more people at risk.

Congenial. This is a rare finding, due to gene mutation parietal cells do not produce intrinsic factor at all or produce it only in small quantities.

Medication. Acid production in the stomach can be stopped by Pantoprazole and to a lesser degree by H2 (histamine receptor 2) blockers. Acid in the stomach is necessary for releasing vitamin B12 from the food substances in the stomach.

History of Pernicious anemia and Vitamin B12.

Before organic chemistry entered the medical field, a careful physical examination and autopsy findings were the only tools known to physicians for determining the cause of an illness. In1799 and 1800s in Scotland and Scandinavian countries, the elderly, particularly the women, were suffering from a slowly progressing fatal disease due to anemia. It was rightly named Pernicious anemia. In 1812 Dr. Comb reported finding atrophic gastritis of a man who died of anemia. Subsequently, between 1945 and 1926, Drs. Addison, Blamer, Whipple, and Minot and Murphy published papers linking pernicious anemia with vitamin B12 deficiency.  In 1934 Drs. Minot, Murphy and Whipple received the Nobel Prize in medicine for their discovery.

Autopsy findings in Subacute Combined Degeneration of the Spinal cord.

Multifocal spongy vacuolated lesions of the dorsal, lateral and corticospinal tracts in the thoracic and cervical sections of the spinal cord, associated perivascular infiltration with foamy macrophages and lymphocyte, and interstitial edema are distinct pathological changes of myelin degeneration.

Diagnosis of SCD.

A good history followed by a neurological examination is all that is needed for making an initial diagnosis which is supplemented by the presence of vitamin B12 deficiency in the nervous tissue, and associated with a typical macrocytic anemia and peripheral neuropathy.

Confirmation of vitamin B12 deficiency.

The blood level of vitamin B12 may or may not be low but serum homocysteine and methylmalonic acid will be high because the conversion of homocysteine to methylmalonic acid and then to S-adenylyl methionine is completed by vitamin B12, acting as a cofactor; in its absence of B12, both homocysteine and methylmalonic acid accumulates in the blood. The blood level of homocysteine is over 15 mcmol/L and methylmalonic acid is >260nmol/L.

Macrocytic anemia.

The red cells are large and oval in shape and the MCV (mean corpuscular volume) volume in macrocytic anemia is on average over 115fL [f=10 to the power of -15] and each red cell has a central pallor. Mild leukopenia and thrombocytopenia also accompany a high MCV. The neutrophils have 6 or more lobed nuclei.

Serum LDH (lactic dehydrogenase enzyme) and unconjugated bilirubin are higher due to a high turnover of the red cell precursors in the bone marrow.

In most cases, MRI of the spine is not essential. In case of any doubts, a bone marrow examination can clinch the diagnosis.

The next step is to identify the etiology of a given case. That involved various tests specific to that case only.

Treatment.

Replacement of vitamin B12 is the key, and the earlier it is done, the earlier recovery is achieved. Various protocols are available, but a standard one is 1000 mg of vitamin B12 is given subcutaneously each week for 6 weeks then once a month for 12 months. If the primary reason for B12 deficiency is not amenable to treatment, then B12 monthly injection is continued for life long. Otherwise, oral B12 therapy may be possible. 

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