It is an uncommon neurological disorder and is associated with pernicious anemia. There is degeneration of posterior and lateral columns of the spinal cord and of peripheral nerves leading to paraesthesia, tingling and numbness in the limbs with sensory loss, impairment of deep sensibility, motor weakness and ataxia.
Vitamin B12 (Cyanocobalamin) plays an important role in DNA synthesis of every biological cell and is essentially required for normal haemopiesis as well as for maintaining integrity of nervous system.
The most common cause of cobalamin deficiency is pernicious anemia in which there is atrophy of gastric mucosa with failure of intrinsic factor secretion. It is an auto immune reaction against gastric parietal cells and is associated with other autoimmune diseases in the body.
Patients of pernicious anemia have abnormal circulating antibodies and the destruction of parietal cells is mediated by complement fixing antibodies. Two types of intrinsic factor antibodies (Type 1 or blocking antibody and Type 2 or Precipitating antibody) inhibit binding of intrinsic factor to Vit B12 and at its receptor site in the ileum.
Prinicious anemia is a disease of elderly and affects both men and women equally. Pathologically there is gastric atrophy with plasma cell and lymphoid infiltration. In the nervous system there is degeneration of myelin sheaths in the upper part of the spinal cord in the ascending tracts and in the lower part.
In the descending tracts. Tracts involved are posterior columns pyramidal and ascending cerebellar tracts as well as peripheral nerves. Degenerative changes include necrotic foci and degeneration where myelin first swells and then disintegrates.
The degenerated areas increase in size, coalesce, reaching the surface of the cord and eventually involve whole of the white matter of the cord. The degeneration first appears in the lower cervical and upper dorsal regions and soon spreads upwards and down wards. When degeneration of perpheraI nerves is severe, muscles may be wasted.
In the gastro intestinal tract there is gastric atrophy of acid and pepsin secretary portion of the stomach.
The symptoms appear insidiously and the first symptom usually is tingling and numbness in the feet as well as coldness and feeling of walking on cotton wool. Uncommonly both upper and lower extremities are involved. Unsteadiness and weakness of the limbs develops.
The paresthesiae which began in the periphery soon spreads upwards and may involve the tmnk, abdomen and chest. Patient complains of a constricting sensation round about. Ataxia leads to poor finger coordination.
Post column involvement leads to loss of postural sensibility, appreciation of passive movements and vibration sensation. Sensory loss in the form of light touch, pin prick, heat and cold over the extremities is in the form of ‘glove and stocking’ distribution. Calves may be tender on pressure.
Because of ataxia, Romberg’s sign is positive. Reflexes are variable; Knee jerks may be lost while in some they are exaggerated. Ankle jerks are diminished or absent. Plantars are extensor Sphincter disturbances in the form of precipitate, retention or incontinence of urine may develop.
Cranial nerves usually are unaffected but in a small percentage of cases optic atrophy may occur and nystagmus may be present. Mental changes in the form of irritability, impaired memory and intellectual capacity, confusional psychosis to dementia in varying degrees may be seen.
Although anemia is an important feature of disease, yet it may be absent throughout the course of the disease and its manifestations may be delayed for long period after sub acute combined degeneration appears. Neurological abnormalities only occur with very low levels of Vit B12 though these may occur in those who are not clinically anemic.
Histamine fast achlorhydria is constantly present. Patient has features of anemia, glossitis (red sore tongue) angular stomatitis malar flush on the face and a yellow tint of skin. There may be oedema, cardiomegaly and hepatosplenomegaly in a few cases.
Peripheral blood shows feabures of megaloblastic anaemia (Hyperchromic macrocytic anaemia). Reticulocyte count is low.Platelet and leucocyte count may be decreased. Peripheral blood film shows marked anisocytosis and poikilocytosis, polychromatophilia.
There is leucopenia with relative lymphocytosis. Neutrophils show hypersegmentation of the nucleus. Bone Marrow examination is diagnostic. It is hypercellular with decreased myeloid / Erythroid ratio and abundant stainable iron. Megakaryocytes may be decreased and show abnormal pathology.
Serum Vit B12 levels are measured using schilling Test. An altemative to this test is whole body counting where a radio active dose of P12 is given orally and total body activity measured. A normal test means retention of 50% or more of 1 ig dose of radio active 812.
Histamine / Pentagastrin fast achlorhydria is present. Marked gastric atrophy can be demonstrated on histopathological studies.
The presence of classical neurological features of polyneuropathy, ataxia, parasthesia and progressive involvement of post and lateral columns in the presence of anemia and achlorhydria is diagnostic.
Differentiale diagnosis is from cases of Tabes Dorsalis. Disseminated Sclerosis, Myelitis and Polyneuritis.
It is mainly Vit B12 in doses of 1000 g daily for a period of 3 weeks and after that in a weekly dose. Patients condition is monitored by clinical improvement, rise in hemoglobin and reticulocyte count.
Neurological symptoms generally take 6-12 months to improve. In advanced cases of sub acute combined degeneration improvement may not take place. Folic Acid is contraindicated in case of subacute. It may harm the patient.
Besides specific treatment, supportive treatment in the form of good diet and analgesics for pain relief may be given.