From Big Medical Encyclopedia

WHETHER DISEASE (D. Leigh, sovr. English neurologist; synonym Subacute necrotizing encephalomyelopathy) — the hereditary disease of the central nervous system which is characterized by the progressing dystrophic defeat of white matter of a head and spinal cord. Treats group of demyelinating diseases of a nervous system.

The etiology and a pathogeny

Assume that the disease is caused by recessive mutation of an autosomal gene in a homozygous state. The question of primary molecular defect caused by a mutation is not solved finally.

At patients exchange of vitamin B is broken 1 , in blood, cerebrospinal liquid and urine the factor suppressing activity of the enzyme catalyzing formation of a tiamintrifosfat (TTF) from ATP and a tiamindifosfat (TDF) in c is revealed. N of page. As a result patients in brain fabric have no TTF at the normal maintenance of TDF and tiaminmonofosfat (TMF). At the same time in a liver almost completely there is no enzyme of a pyruvatecarboxymanhole catalyzing transformation pyroracemic to - you in oxalacetic — the initial stage of a gluconeogenesis, in the course to-rogo substrate for a cycle dicarbonic to - Krebs's t is formed. It is possible that both biochemical, defect are interconnected or exist various on an etiology and a pathogeny of a form.

The pathological anatomy

Gistol, a picture of a brain reminds the changes observed at acute alcoholic encephalopathy of Vernike (see. Alcoholic encephalopathies ). In brain fabric the symmetric centers of demyelination with secondary change of axons which are localized preferential in the field of a brainstem and the III ventricle, to a lesser extent — in a spinal cord are found. Bodies of neurons remain rather safe. In sites with the expressed disintegration of a myelin perivascular infiltration is observed, edges in combination with necrotic process causes gray-brown coloring of the centers. The reactive gliosis and proliferation of a microglia are expressed moderately. At longer current spongy regeneration of a brain, an atrophy of a cerebellum and posterolateral departments of a spinal cord is observed.

In muscles are found dragged - a pas, hl. obr. the first histologic type, containing excess of the material which is painted in bright red color trikhromovy dye of Gomori — so-called violent-red fibers, an origin to-rykh as believe, it is connected with disturbance of mitochondrions. At a submicroscopy subsarcolemmic accumulations of the mitochondrions increased in the sizes containing dense spherical little bodies and rectangular paracrystal inclusions in membranes of cristas come to light.

At nek-ry patients find specific vacuolated cells in marrow.

A clinical picture

Distinguish 2 options of clinical disease. The early children's fast-progressing form is characterized by emergence a wedge, symptoms at children of the first two years of life with a lethal outcome in 1 — 2 years. The current is usually subacute.

The first symptoms of a disease are anorexia, vomiting, disturbance of suction and swallowing. The progressing pyramidal disturbances up to a tetraplegia are observed, at the same time the muscle tone is usually lowered. Patients cease to move, stand, sit and hold the head. The ophthalmoplegia, paralysis of mimic muscles, the ataxy, deafness and an atrophy of an optic nerve leading to a blindness develops. At certain patients signs of defeat of extrapyramidal system in the form of muscular rigidity, a tremor, an athetosis, etc. are observed. There are cardiovascular disturbances caused by a cardiomyopathy. In an end-stage consciousness is broken, there are respiratory frustration which are, as a rule, a cause of death. At more high-quality form symptoms of a disease appear at the age of 10 — 15 years.

The diagnosis

Intravital establishment of the diagnosis presents great difficulties. The diagnosis can be confirmed with detection in biol, liquids of inhibitor TDF-ATF-fosfotransferazy, a hypoglycemia and increase in content in blood serum milk, pyroracemic to - you and alanine. The general hyper aminoaciduria or increase in excretion of alanine, a tsistationin and a histidine are characteristic. In cerebrospinal liquid increase in protein content is defined. At patients with absence in a liver pyruvatecarboxymanholes decrease of the activity of a fosfofruktokinaza of muscles is possible. At nek-ry patients find specific vacuolated cells in marrow. On EMG removed by means of needle electrodes signs of primary and muscular defeat come to light.

Differential diagnosis carry out with a tumor of a trunk of a brain, leukoencephalites (see) and leukodystrophy (see), amaurotic idiotiya (see), disease beriberi (see), encephalomyelitis (see) and encephalopathies (see).


Is shown purpose of high doses of thiamin (to 1500 mg a day), lipoic to - you (0,7 mg on 1 kg of weight intramusculary 3 times a week), glutaminic to - you (to 150 mg there are each three hours inside), vitamin B 6 (on 50 mg 4 times a day). Depending on weight of a course of a disease treatment is carried out constantly or discontinuous courses.

The effect of each of components of complex treatment at certain patients is various. The positive effect is expressed in a wedge, remissions sometimes up to 2 years, followed by decrease in levels milk and pyroracemic to - t in blood and disappearance of inhibitor of TDF-ATP-phosphorylase from biol, liquids.

Forecast in the absence of therapy adverse; pathogenetic treatment promotes suspension of process and can lead to nek-rum to improvement.

See also Demyelinating diseases .

Bibliography: Spirichev V. B. and Barashnev Yu. I. Inborn disturbances of exchange of vitamins, page 24, M., 1977; Leigh D. Subacute necrotizing encepha-lomyelopathy in an infant, J. Neurol. Neurosurg. Psychiat., v. 14, p. 216, 1951.

L. O. Badalyan.