Funicular myelosis

Funicular myelosis, neuroanemic syndrome or funicular myelosis syndrome are referred to as myelopathies, since it is the result of a pathological process of the central nervous system, such as the destruction of the protective myelin sheath of spinal nerve fibers, which leads to subacute combined degeneration of the spinal cord.

Epidemiology

There are no data on the prevalence of funicular myelosis, but it is known that it usually affects people over forty years of age, and that in 95% of patients, the etiological factor of this syndrome is pernicious anemia, which is autoimmune in nature: the presence of antibodies to parietal cells of the stomach and to internal Castle factor, which ensures the absorption of vitamin B12 in the ileum.

And, according to international statistics, 1-2% of all reported cases of anemia are pernicious anemia.

In European countries, vitamin B12 deficiency is observed in 5-46% of the elderly, and in Latin America - in 60% of the adult population. Also, 20-85% of vegetarians suffer from cobalamin deficiency.

Causes funicular myelosis

The main causes of funicular myelosis - demyelination of the nerve fibers of the funiculus or spinal cord columns - is a  lack of vitamin B12  (cobalamin) in the body. [1]

Also, disturbances in the metabolism of vitamin B12  (in particular, its malabsorption) and megaloblastic anemias associated with a deficiency of folic acid and cobalamin  can lead to this pathology  .

How are pernicious or B12-deficient anemia and funicular myelosis related? Due to its composition, cobalamin plays an important role in many biological processes and is necessary for the transformation of fatty acids, some amino acids and folic acid; for the biosynthesis of DNA, nucleotides and methionine; for the maturation of red blood cells and the growth of axons of neuronal cells.

This vitamin contributes to the maintenance of the normal function of the nervous system, since it is a cofactor in the production of the main protein of the nerve fiber sheath - myelin by Schwann cells and oligodendrocytes.

Risk factors

Experts see the risk factors for the development of funicular myelosis in chronic deficiency of cobalamin in the body, the likelihood of which, in turn, increases with  low stomach acidity ; hypoacid, atrophic or anacid gastritis with  achlorhydria , as well as when part of the stomach is removed. And this is due to the fact that vitamin B12 associated with the protein of food is released in the stomach - under the action of hydrochloric acid and the protease produced by the cells of the stomach - pepsinogen.

Factors that increase the risk of B12 deficiency with the development of neurological symptoms include chronic liver disease (since it is there that stores of this vitamin in the form of transcobalamin I are stored), as well as  Crohn 's disease, Addison's disease, hypoparathyroidism and pancreatic insufficiency,  Zollinger-Ellison syndrome , celiac disease, autoimmune systemic scleroderma with gastrointestinal tract damage, malignant neoplasms (including lymphoma),  diphyllobothriasis . [2]

Pathogenesis

Explaining the pathogenesis of degenerative changes in the  spinal cord , it should be noted that neurological manifestations in this condition are due to the defeat of the paired posterior (funiculus dorsalis) and lateral (funiculus lateralis) cords of the white matter of the spinal cord, consisting of processes (axons) of neurons. These cords are conductive associative, ascending (afferent) and descending (efferent) pathways along which the corresponding impulses pass between the spinal cord and the brain. That is, axons are affected both in the ascending pathways of the posterior column and in the descending pyramidal pathways. [3]

Demyelination of the cords with a deficiency of vitamin B12 is associated with the activation of stress in the endoplasmic reticulum (reticulum) of cells, which can be caused by an increase in the phosphorylation of kinases (IRE1α and PERK) and translation initiation factor 2 (EIF2), as well as the expression of activating transcription factor 6 (ATF6). As a result, there is a decrease in translation initiation (protein synthesis by the ribosome on messenger RNA) and inhibition of total protein synthesis, which leads to the arrest of the cell cycle and acceleration of apoptosis of myelin cells. [4]

In addition, the production of abnormally altered melanin - with a lower lipid content - is possible due to the increase in the mitochondrial level of the coenzyme methylmalonyl-CoA due to a lack of cobalamin, which interferes with the synthesis of fatty acids and causes the accumulation of methylmalonic acid, which leads to oxidative stress in cells.

Read also -  Pathogenesis of vitamin B12 deficiency

Symptoms funicular myelosis

There are such types or forms of funicular myelosis: posterior columnar sensory ataxia or funicular myelosis with damage to the posterior cords of the spinal cord; pyramidal funicular myelosis - with damage to the funiculus lateralis, as well as mixed (with damage to the posterior and lateral cords). [5]

There are also three stages or periods in the development of pathology. The first signs of the prodromal period of subacute combined degeneration of the spinal cord are sensations of numbness and tingling (paresthesia) in the tips of the toes, occasionally in the toes and hands; decrease in their sensitivity. Over time, these sensations spread to the feet and hands. Patients complain of muscle weakness, frequent loss of balance and changes in gait.[6]

As the progression progresses, in the second stage, symptoms such as ataxia (impaired coordination of movements), changes in postural sensitivity, a decrease in some tendon reflexes, loss of deep sensitivity, stiffness of movements of the lower extremities due to spastic paresis, difficulty walking and immobility of the patient are observed. Vision may deteriorate (due to pupillary disorders). [7]

At the third stage, a disorder of urination (in the form of retention or incontinence of urine) and defecation (manifested by constipation) may be added to the existing symptoms. Pronounced changes in the psyche are not uncommon.

Also see -  Symptoms of Spinal Cord Damage

Complications and consequences

The most significant consequences and complications of funicular myelosis: neurological disorders, progressing to lower spastic paraparesis (paraplegia), and mental changes - up to partial cognitive dysfunction.

In severe cases, damage to the gray matter and axons of the anterior horn of the spinal cord and cortical parts of the brain is possible. [8]

Diagnostics funicular myelosis

Routine diagnosis begins with recording the existing symptoms, examining the history, examining the patient, and  examining reflexes .

Blood tests are taken: general, for the level of vitamin B12 and folates, homocysteine and methylmalonic acid, for the presence of antibodies to intrinsic factor (AIFAB) and parietal cells of the gastric mucosa (APCAB), etc.

Instrumental diagnostics includes  electroneuromyography  and MRI of the corresponding parts of the spine. [9]

Differential diagnosis

To exclude radiation or herpes myelitis, amyotrophic lateral and multiple sclerosis, polyneuritis, spondylogenic myelopathy, HIV vacuolar myelopathy, late form of neurosyphilis (tabes dorsum), sarcoidosis, hereditary syndromes and various motor-sensory polyneuropathies, astrocytoma, leukoenopathies, diagnostics are performed.

Treatment funicular myelosis

Treatment is aimed at stopping anemia and the process of demyelination of axons by intramuscular injections of vitamin B12 (cyanocobalamin) together with other B vitamins.More information in the article -  Treatment of vitamin B12 deficiency [10]

Prevention

Prolonged vitamin B12 deficiency leads to irreversible damage to the nervous system, therefore, the diet should have enough foods containing cobalamin. What foods contain it, in detail in the publication -  Vitamin B12 .

Also, if possible, the causes of vitamin B12 deficiency should be eliminated  , although the predisposition to pernicious anemia is inherited in an autosomal dominant way.

Forecast

What determines the prognosis of funicular myelosis? From the stage of the syndrome at the time of going to the doctor, the severity of the symptoms and the effectiveness of treatment. Without treatment, patients' condition worsens, but therapy can relieve paresthesia and ataxia. However, in half of the cases in the late stage,  it is almost impossible to cope with  spastic paraplegia .