LEUKODYSTROPHY (Greek leukos white + dystrophy) — group of hereditary diseases at which process of myelination is broken. The term was offered in 1928 by M. Bilshovsky and R. Henneberg instead of the term «diffusion scleroses» applied earlier.
Main mode of inheritance of L. — autosomal and recessive, also the recessive inheritance linked to a floor is possible. Along with sporadic family cases are quite often described, in separate families only boys are ill. Cases of a consanguineous relation of parents of patients meet. Parents of sick L. phenotypical are healthy.
At the heart of a pathogeny of L. genetically determirovanny euzymatic defect causing disturbance of a miyelogenez and exchange of abnormally constructed myelin lies; synthesis of a myelin is originally broken (dismiyelinization).
The atrophy of a brain quite often with the centers of a softening of various prescription is characteristic of these diseases. The general patomorfol, feature of L. extensive, rather symmetric dystrophic defeat of white matter of both cerebral hemispheres, a cerebellum, spinal cord is. Initially suffer and myelin covers, often are exposed to the greatest changes, on axial cylinders to a lesser extent change. At gistol. a research the multiple merging centers of demyelination of pyramidal, extrapyramidal, cerebellar conduction paths and associative fibers are found. Demyelination can be combined with spongiosas. In white matter at biochemical, a research reduction of lipids is found. Products of fine-grained disintegration of a myelin — lipids are postponed in and out of nervous cells of different departments of c. the N of page, comes to light a reactive hyperplasia of gliozny fabric with formation of gliozny hems. Lipids collect in internals, hl. obr. in kidneys and a liver.
To a lesser extent, than white matter, suffers gray matter, in Krom sites of death and regeneration of nervous cells are found. In a varying degree in patol, process peripheral nerve fibrils are involved. Unlike leukoencephalites (see), shout a leukodystrophy there are no inflammatory infiltrates.
Most often L. begin at early children's age, is more rare in youthful, cases and at adults are sometimes observed. To a disease children usually develop normally. Change of behavior of the child can be his first manifestation — it becomes sluggish, whining, loses interest to surrounding, a hyperexcitability is noted from time to time. Soon appear and quickly focal frustration of a nervous system according to its multiple defeat develop. Wedge, picture L. it is characterized by a big variety of symptomatology. At most of patients various motive frustration — spastic, sluggish paresis, paralyzes are observed (see. Paralyses, paresis ), ataxy (see), koordinatorny frustration, intentsionny trembling (see), nystagmus (see), epileptic seizures — the general and jacksonian (see. Epilepsy , Jacksonian epilepsy ), Extrapyramidal frustration — a syndrome parkinsonism (see), hyperkinesias (see) and often myoclonic twitchings in different muscular groups, including in language. One of characteristic symptoms is the partial or full atrophy of nipples optic nerve (see), as a rule, followed by loss of sight; hearing is broken, dementia accrues. Various vegetative frustration, attacks of a hyperthermia are observed. In an end-stage of a disease there is a cerebrate rigidity (see), bulbar frustration. Patients perish in different terms from the beginning of a disease (mostly in several months), being in a condition of a cachexia, most often from aspiration pneumonia and other intercurrent diseases, sometimes during the epileptic status.
At L. in blood, urine, cerebrospinal liquid changes from which change of maintenance of lipids, and also amino acids is especially important are found expressed biochemical.
According to some authors, in blood serum antibodies to a myelin, in cerebrospinal liquid — unsharply expressed proteinaceous and cellular dissociation can be found. In material of a biopsy of cutaneous nerves disintegration of a myelin is possible.
At electroencephalography (see) the expressed nonspecific changes — absence or disorganization of an alpha rhythm, existence a theta and the delta of waves come to light. At electromyography (see) delay of speed of carrying out impulses on nervous trunks is noted.
L. are sometimes combined with other hereditary diseases — a fenilketonuriy, amaurotic idiocy.
Diagnosis presents great difficulties, especially at early stages of a disease, it is quite often put only on section. Question of a possibility of L. arises in cases of the multifocal progressing defeat of c. N of page at the child in the presence in a family of the patient with this disease.
In diagnosis of L. the comprehensive examination of the patient including biochemical, and morfol, a blood analysis, urine, cerebrospinal liquid, a research of material of a biopsy of cutaneous nerves is necessary.
Treatment symptomatic. Appoint hemotransfusion and plasmas, fabric extracts, anticonvulsant, dehydrational means, vitamin therapy. At Gallervorden's disease — Shpattsa noticeable improvement gives alpha DOF'S use.
If in a family there are sick L., it is recommended to abstain from a child-bearing. Pre-natal diagnosis is in some cases applied by means of amniocentesis (see).
Depending on age, in Krom the disease, nevrol began. symptoms, data of a biochemical and pathoanatomical research allocate a little nozol, forms L., from which are most studied metachromatic L. Greenfield — Sholtsa, globoidal and cellular by L. (Krabbe's disease), sudanophil L. (Pelitseus's disease — Mertsbakhera), Gallervorden's disease — Shpattsa.
Separate forms watering can of dystrophies
Metachromatic Greenfield's leukodystrophy — Sholtsa (synonym late infantile leukodystrophy). This disease was described W. Scholz in 1925 and Y. G. Greenfield in 1933. It is inherited on autosomal recessively type. Inborn deficit of activity of enzyme of a tserebrozidsulfataza (arylsulphatase A) is the cornerstone of a pathogeny that leads to the progressing extensive demyelination and spongy dystrophy of tissue of brain and to adjournment in the form of granules of products of exchange — sulfatides — in nervous cells, nerve fibrils, a glia of different departments of c. N of page, hl. obr. subcrustal nodes, as well as in peripheral nerves, a retina of eyes, tubules of kidneys, leukocytes of blood.
In tissue of a brain the maintenance of lipids is reduced and the level of sulfatides is rather increased. At a lab. researches sharp reduction or lack of arylsulphatase in leukocytes, increase in excretion of sulfatides with urine is found.
Characteristic morfol, feature of a disease of Greenfield — W. Scholz consists that at gistol, a research sulfatidny granules are painted in brown color though dye blue toluidine (a phenomenon of a metachromasia) is applied; at Austin's test which is important for diagnosis metachromatic L., the urocheras of the patient at addition of blue toluidine is painted in brown color.
The disease most often begins at the age of 1 — 3 years though there are cases of earlier and later beginning. The first symptoms of a disease are atactic frustration, a muscular atony with decrease in tendon jerks. Further there are spastic paresis, paralyzes, epileptic seizures, dementia accrues, the cerebrate rigidity, a cachexia develops.
Sometimes the disease is shown in the form of a polyneuropathy (see. Polyneuritis ) without symptoms of defeat of c. N of page. In these cases for the purpose of diagnosis material of a biopsy of cutaneous nerves is investigated, in Krom disintegration of a myelin and metachromatic granules are found.
Life expectancy of most of patients — from several months to 1 year, sometimes up to 10 and more years. Depending on age, in Krom the disease begins, allocate inborn, children's, youthful and adult forms metachromatic to L.
Globoidal and cellular leukodystrophy Krabbe was described (To. H. Krabbe) in 1916; the author (Krabbe's disease) is called by name.
The disease is transmitted on autosomal recessively type and recessive, linked to a floor. Boys are ill only.
The pathogeny is connected with insufficiency or lack of a beta galactosidase, than disturbance of metabolism of cerebrosides is caused.
N. I. Malone with coauthors (1975) investigated the maintenance of a beta galactosidase at members of one family. At children with Krabbe's disease it was absent, and at their parents — phenotypical healthy geterozigot on a gene of this disease — its activity was reduced in comparison with control group. This observation is of interest from the point of view of detection of heterozygosity. On autopsy the considerable atrophy of a brain with sites of consolidation in subcrustal white matter owing to an astrocytic gliosis is found. At microscopic examination the centers of spongy dystrophy, hl come to light along with widespread demyelination. obr. in top coats of brain bark and in U-shaped associative fibers. Gistopato of l. feature of a disease of Krabbe are large one - and multi-core globoidal (spherical) cells adventitsialno of a histiocytic origin.
The disease begins in the first months after the birth, later beginning was in some cases noted (in 3 — 6-year age). The first a wedge, displays of a disease are expressed by frequent short-term attacks of rigidity with opisthotonos (see), the atrophy of disks (nipples) of optic nerves with loss of sight quickly develops, epileptic seizures, myoclonias in different muscular groups are observed, swallowing is broken, dementia develops, edges can reach degree of an idiocy, in an end-stage there is a cerebrate rigidity. Patients usually perish several months later from an onset of the illness during the epileptic status or from aspiration pneumonia.
Sudanophil leukodystrophy it was described by F. Pelizaeus in 1885, L. Merzbacher in 1908; authors are called by name (F. Pelizaeus's disease — L. Merzbacher). Mode of inheritance of a disease — autosomal and recessive. Both floors get sick equally often. There are instructions on a possibility of dominant inheritance. At gistol, a research of a brain it is found along with the rarefied myelin fibers it is a lot of quite remained. Characteristic gistopatol. a symptom of a disease of F. Pelizaeus — L. Merzbacher is coloring by Sudan of III in red color perivascular deposits of the broken-up myelin in different departments of a brain. At biochemical, a research decrease in tissue of a brain of cholesterol, sphingomyelin, cerebrosides is noted.
The disease begins at different age, a thicket in chest, can sometimes be inborn. Its first symptoms are the ataxy, a nystagmus, trembling of the head, intentsionny trembling, a scanning speech, squint. Further the central paresis, paralyzes of extremities, an atrophy of nipples of optic nerves join, it is frequent only temporal half, in most cases intellectual disturbances are expressed unsharply.
Pelitseus's disease — Mertsbakhera has an optimum current in comparison with other L. Patients can live decades, process develops slowly, remissions are possible.
Gallervorden's disease — Shpattsa (a synonym the progressing rigidity). In 1922 Mr. Gallervorden and Shpatts (J. Hallervorden, H. Spatz) described a family, in a cut 5 patients were this disease. A mode of inheritance — autosomal and recessive. Pathoanatomical changes at Gallervorden's disease — Shpattsa are most expressed in subcrustal nodes. Their feature is the increased quantity of a ferriferous pigment in a pale sphere and black substance of a brain thanks to what these educations have brown coloring. In giperplazirovanny gliozny fabric the cells with a large kernel reminding Alzheimer's glia meet. At biochemical, a research of tissue of brain disturbance of lipid metabolism, iron, catecholamines is found.
The disease begins in 9 — 10 years more often, however also adults get sick. In a wedge, a picture of a disease the main place is taken by Extrapyramidal motive frustration. The first symptoms are hyperkinesias of athetotic, torsionnodistonichesky character, an akinetiko-rigid syndrome (see. Trembling paralysis ), regarding cases atactic frustration join. The changes in the emotional and intellectual sphere of various degree of manifestation mostly moderate can be observed. The disease which is slowly progressing.
Spongy degeneration of white matter (synonym: Kanavan's disease, Kanavan's disease — Van-Bogart — Bertrán).
Mode of inheritance — autosomal and recessive and recessive, linked to a floor: boys get sick almost only. The disease arises vnutriutrobno and is clinically shown in the first days after the birth. At a pathoanatomical research puffiness of brain fabric, spongiosas and demyelination of white matter of a brain with decrease in cerebrosides and sphingomyelin is found.
Often first symptoms of a disease are epileptic seizures; the child is sluggish, sleepy, dementia, paresis of legs quickly develops, the nystagmus, squint appears, hearing, and also sight owing to an atrophy of disks of optic nerves is lost, swallowing falls apart.
The course of a disease which is quickly progressing in an end-stage is observed a cerebrate rigidity.
Life expectancy does not exceed two years. Patients perish during the epileptic status or from an intercurrent disease.
Leukodystrophy with a diffusion fibrous formation of Rosenthal (Alexander's disease) meets very seldom.
At patol, a research of c. the item of page is found increase in a brain, widespread demyelination with focal softenings of different size, accumulation of a hyalin is especially characteristic described by Rosenthal (S. of Rosenthal).
The disease begins at early children's age, the main a wedge, its manifestations are hydrocephaly, quickly accruing dementia, epileptic seizures, spastic paralyzes.
Life expectancy of sick no more than two years.
Bibliography: Badalyan L. O., Tabolin V. A. and Veltishchev Yu. E. Hereditary diseases at children, page 90, M., 1971; Gusev E. I. Clinical and biochemical studying of some hereditary diseases of a metabolism with defeat of a nervous system, Zhurn, a neuropath, and psikhiat., t. 71, No. 10, page 1475, 1971; Kalmykova L. G. Hereditary heterogeneity of diseases of a nervous system, page 52, M., 1976; Makkyyusik V. A. Ancestral features of the person, the lane with English, page 445, M., 1976; Handbook of clinical neurology, ed. by P. J. Vinken a. G. W. Bruyn, v. 10, Amsterdam a. o., 1975; P o s e r G. M. Leukodystrophy and the concept of dysmyelination, Arch. Neurol. (Chic.), v. 4, p. 323, 1961, bibliogr.
P. A. Tkachyov.