Funicular myelosis

Funicular myelosis, neuroanemic syndrome or funicular myelosis syndrome are classified as myelopathies, as they are 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 has an autoimmune nature: the presence of antibodies to the parietal cells of the stomach and to the intrinsic factor of Castle, which ensures the absorption of vitamin B12 in the ileum.

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

In European countries, vitamin B12 deficiency is observed in 5-46% of elderly people, 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 – are a lack of vitamin B12 (cobalamin) in the body. [ 1 ]

Also, this pathology can be caused by disturbances in the metabolism of vitamin B12 (in particular, its malabsorption) andmegaloblastic anemia associated with a deficiency of folic acid and cobalamin.

How are pernicious or B12-deficiency 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 helps maintain normal function of the nervous system, as 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 risk factors for the development of funicular myelosis in chronic cobalamin deficiency in the body, the likelihood of which, in turn, increases with low stomach acidity; hypoacid, atrophic or anacid gastritis with achlorhydria, as well as with removal of part of the stomach. And this is due to the fact that vitamin B12, bound to food protein, is released in the stomach - under the action of hydrochloric acid and protease produced by stomach cells - pepsinogen.

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

Pathogenesis

Explaining the pathogenesis of degenerative changes in the spinal cord, it is necessary to note that neurological manifestations in this condition are caused by damage to the paired posterior (funiculus dorsalis) and lateral (funiculus lateralis) funiculi of the white matter of the spinal cord, consisting of the processes (axons) of neurons. These funiculi are conducting 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 cords in vitamin B12 deficiency is associated with activation of endoplasmic reticulum (reticulum) stress, which can be caused by increased phosphorylation of kinases (IRE1α and PERK) and translation initiation factor 2 (EIF2), as well as expression of activating transcription factor 6 (ATF6). As a result, there is a decrease in translation initiation (protein synthesis by the ribosome on the messenger RNA) and inhibition of general protein synthesis, which leads to cell cycle arrest and acceleration of myelin cell apoptosis. [ 4 ]

In addition, abnormally altered melanin may be produced – with a lower lipid content – due to an increase in the level of the coenzyme methylmalonyl-CoA in the mitochondria caused by 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

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

Three stages or periods of pathology development are also distinguished. The first signs of the prodromal period of subacute combined degeneration of the spinal cord are numbness and tingling (paresthesia) in the tips of the toes, occasionally in the fingers and toes; decreased 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 it progresses, in the second stage, symptoms such as ataxia (impaired coordination of movements), changes in postural sensitivity, decreased tendon reflexes, loss of deep sensitivity, stiffness of the lower limbs 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, the existing symptoms may be supplemented by urinary disorders (in the form of urinary retention or incontinence) and defecation disorders (manifested by constipation). Pronounced mental changes are not uncommon.

See also - Symptoms of Spinal Cord Injury

Complications and consequences

The most significant consequences and complications of funicular myelosis are 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 the cortical regions of the brain is possible. [ 8 ]

Diagnostics funicular myelosis

Standard diagnostics begin with recording the existing symptoms, studying the anamnesis, examining the patient and studying reflexes.

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

Instrumental diagnostics include 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 neurosyphilis (tabes dorsalis), sarcoidosis, hereditary syndromes and various motor-sensory polyneuropathies, astrocytoma, ependymoma, leukoencephalopathy, differential diagnostics are performed.

Treatment funicular myelosis

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

Prevention

Long-term vitamin B12 deficiency leads to irreversible damage to the nervous system, so the diet should contain enough products containing cobalamin. Which 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 manner.

Forecast

What does the prognosis of funicular myelosis depend on? On the stage of the syndrome at the time of contacting a doctor, the severity of symptoms and the effectiveness of treatment. Without treatment, the patient's condition worsens, but therapy can relieve paresthesia and ataxia. However, in half of the cases at a late stage, spastic paraplegia is almost impossible to cope with.