From Big Medical Encyclopedia

TUBEROUS SCLEROSIS (sclerosis tuberosa; lat. tuberosus hilly; sclerosis; synonym: Burnevill's disease, Burnevill's disease — J. J. Pringle) — the hereditary progressing disease from group of fakomatoz which is characterized by the combined defeat of a nervous system, skin, eyes, bone and endocrine systems, internals.

It is for the first time described in 1863 by F. Rek-lingkhauzen. In 1880 Mr. Burnevill (D. - M. Bourneville), having allocated this disease in a separate nosological form, entered the term «tuberous sclerosis» and in details described early nevrol. symptoms, changes of skin, etc. In 1890 Mr. J. J. Pringle in detail studied adenomas of sebaceous glands of face skin and emphasized that they are characteristic of T. page.

According to Penrose (L. S. Penrose), T. the page in the general population meets frequency about 1:600 000, among patients with various degree of mental retardation — 1:30 000.

Etiology. In development of T. pages assign a big part to genetic factors. Family forms of a disease are quite often observed in several generations. The T is inherited. page on autosomal dominantly type with incomplete penetrance of a mutant gene (see Penetrantpnost of a gene). The twin method (see) researches finds high concordance on symptoms of a disease in monozygotic twins.

Pathogeny. It is supposed that genetically caused disturbance of development of formative cells leading to ektomezodermalny displaziya with formation of tumorous nodes, inclined to neoplastic transformation, in c is the cornerstone of a disease. N of page and internals.

Pathological anatomy. A brain at T. by page it is usually increased in comparison with age norm, however sometimes observe also a nanocephalia (see). Cerebral cortex on separate sites of whitish-yellowish color of various size and bigger, in comparison with surrounding fabric, density. In the center of sites of the changed bark there are superficial retractions, in to-rye vessels plunge. On cuts of cerebral hemispheres in bark various quantity fungoid opukhole-

Fig. I is found. Macrodrug of the right cerebral hemisphere (a medial surface) at a tuberous sclerosis: shooters specified multiple hillocks in a cerebral cortex and a side ventricle.

similar formations, or hillocks (fig. 1); their identification formed the basis of the name of a disease. Single or multiple grayish hillocks the size from a pin head to several centimeters in the diameter also find in white matter of cerebral hemispheres, in side ventricles, a thicket near a tape of a thalamus, is more rare in front and lower horns of side ventricles, in a silviyevy water supply system (a water supply system of a mesencephalon, T.) and in the fourth ventricle. In nek-ry cases of T. pages of change are available also in a cerebellum. Opukholepodobny educations can break outflow of cerebrospinal liquid from ventricles and lead to development of internal hydrocephaly (see). These educations usually obyzvestvlena, and the centers of calcification are located more often in the depth of a hillock.

At gistol. a research of «tuberous» sites in a cerebral cortex find atypical, a bizzare shape large neurons (fig. 2), axons to-rykh quite often go to the surface of bark, are weaved into balls, are implemented into walls of vessels. In bark find also large atypical cells with one-two puzyrkovidny kernels, cytoplasm to-rykh during the coloring by thionine gets pale blue coloring. These cells as it is established modern immunol. researches, are also neurons, but not astrocytes as it was supposed earlier. In a cerebral cortex there are also disturbances of normal cytovery tectonics with lack of neurons, their atrophy and vacuolation. The cerebral cortex is indistinctly delimited from white matter, in it the expressed gliosis (see), the argentofilny educations, granular spheres located on the course of vessels are defined (nek-ry researchers connect emergence of granular spheres with the destructive processes caused by frequent epileptic seizures). Walls of vessels of a brain are thickened, symptoms of fibrosis and gialiio-for are noted (see). Soft and web covers of a brain are thickened, in the last the quantity of melanophores is increased. In the hillocks located in white matter of cerebral hemispheres and a cerebellum find single large atypical cells with a puzyrkovidny kernel, and also gnezdny accumulations of cells with hyperchromic kernels and the wrinkled cytoplasm (fig. 3). Opukholepodobny educations in a brain of patients I.e. contain in one cases the large roundish cells similar to atypical neurons, in others — roundish or spindle-shaped cells with the oval or extended kernels or multinucleate cells. These educations on gistol. to a structure are similar to neurinoma (see), subependimarny astrocytomas (see), ependymomas (see). The nodes found in an eyeglobe most often are gliomas. Also focal calcifications in a choroid of an eyeglobe, its angioma (see), malformations of an eye are described.

In a myocardium of sick T. villages also find the opukholepodobny nodes which are quite often located in the field of the carrying-out system of heart or growing in a cardial cavity and having a structure of a lipoma (see), fibrolipomas, rhabdomyomas (see). Observations of a rabdomiomatoz of a myocardium are known (accumulations of atypical cells in a myocardium). In kidneys at T. villages find small and huge gamartoma (see), capillary angiomas, and also other malformations of vessels and various departments of nephron. Also lipomyomas and «sarkomatozny fabric» in limf, nodes, lipomyomas, angiomyolipomas are described (see Kidneys, t. 25, additional materials) and angiomatous adenomas (see the Angiomatosis) in a liver and a spleen, cysts and myomatous educations in lungs, accumulations of fatty and atypical epithelial cells in a thyroid gland, an aplasia and a hypoplasia of testicles, lipomatous educations in nadpo-

Fig. 2. Microdrug of a cerebral cortex at a tuberous sclerosis: the arrow specified large atypical neuron; impregnation across Bilshovsky; x 4 00.

Fig. 3. Microdrug of white matter of a cerebral hemisphere at a tuberous sclerosis: 1 ~ large atypical

cell; 2 — gnezdny accumulation of cells with the wrinkled cytoplasm and hyperchromic kernels: coloring hematoxylin -

eosine; x 4 00.

chechnik, adenomas (see) from cells of pancreatic islands, accumulation of cells of a multilayer flat epithelium in a front share of a hypophysis, a cyst in its back share, etc.

Clinical picture. The disease develops at children of 1 — 3 years, begins usually with developing of epileptic seizures (see Epilepsy) polymorphic character: small, big, with generalized or focal spasms (see). Small epileptic seizures of a different form (absentias epileptica, myoclonic, akinetic, propulsive) in process of development of a disease pass into big convulsive attacks with a loss of consciousness. There are focal motor, touch attacks, convulsive attacks as jacksonian epilepsy (see). Early symptoms is also lag of mental development (see Oligophrenias) and a behavior disorder. Decrease in intelligence reaches degree of a deficiency of intellect and even an idiocy. There is an accurate correlation between intellectual degradation and weight of epileptic attacks. In nevrol. the status defeats cherepnomozgovy come to light (cranial, T.) nerves, a pyramidal hemiparesis (see the Hemiplegia), ekstrapirampd-ny hyperkinesias (see), etc. is more often oculomotor, block and taking away. Along with it there can be hypothalamic frustration:

vegetatively trophic, endocrine and exchange (diabetes mellitus, premature sexual development, hypothyroidism, dysfunction of pituitary and adrenal system). Skin manifestations arise after psychological disturbances. For T. the page is characteristic emergence of adenomas of the sebaceous glands (see Adenoma of sebaceous glands) symmetrized in the form of a butterfly on a face is preferential in wings of a nose, on cheeks, a chin (fig. 4); adenomas can sometimes extend to a neck, area of nadplechiya. Ochi happen odi-

Fig. 4. Face of the patient with a tuberous sclerosis: multiple adenomas of sebaceous glands are visible.

night or multiple, have an appearance of small or large papules of yellow or pink color, the dense, reminding grains sagos. Along with adenomas on skin find spots of color of coffee with milk (see the Melanosis), dense sites of «pebble-leather», an angiofibroma (see), angiectasias (see), hyper - or hypopigmentation (see Pigmentation). Angiofibromas and angiectasias can arise also on mucous membranes. At sick T. pages often come to light dizembriogenetichesky changes of bone system, napr, spina bifida (see). The tumorous educations and cysts found in internals (heart, a liver, kidneys) clinically can a long time or not be shown or shown by nonspecific symptoms of defeat of this body, napr, a hamaturia at all (see) at damage of kidneys, etc.

At Ophthalmolum. a research establish specific changes on an eyeground: in the field of an optic disk — the single nodular gamartoma or multiple small knots of gray-yellow color reminding fruits of a mulberry; in a retina — changes of a pigmented layer. Progressing patol. changes of eyes leads to glaucoma and a blindness.

The disease progressing: the central paralyzes (see Paralyses, paresis), extrapyramidal, hypothalamic, neuroendocrinal, mental disorders appear and accrue. Especially bystry progressing of a disease occurs in the pubertal period.

The diagnosis is based on emergence of epileptic seizures of polymorphic character at early children's age, lag of intellectual development, an arrest of development of motor and speech functions, existence of adenomas of sebaceous glands on a face and other characteristic changes of skin, change on an eyeground, progressing of a disease, the family nature of a disease. At a X-ray analysis of a skull find an osteosclerosis (see) preferential calvaria, symptoms of intracranial hypertensia and a petrifikata (see) in structures of a brain, to-rye by the form remind the centers of calcification at toxoplasmosis and a cytomegaly. The correct and early diagnosis help the given computer tomography (see the Tomography computer) finding changes of system character in a brain, kidneys, a liver, heart, etc. At a computer tomography of a brain reveal multiple tumorous educations, expansion of ventricles, hydrocephaly of various expressiveness, a petrifikata, to-rye are localized in bark, is more often in frontal and parietal shares, in the third and side ventricles. Rentgenol. the research of a backbone, pelvic bones, extremities reveals the centers of an osteosclerosis, a thickening of a periosteum, cystiform educations in a periosteum of bones of hands and legs, osteoporosis (see) metacarpal and plusnevy bones, etc.

At elektrofiziol. a research find focal or diffusion changes of EEG of epile-ptoidny character (see Elektroentsefalografiya). Cerebrospinal liquid is usually not changed, except for cases when at severe damages of a brain hydrocephaly, wet brain, the epileptic status and other states complicating disease develop.

The differential diagnosis carry out with a neurofibromatosis (see), an entsefalotrigeminaljny angiomatosis (see) Gippel's disease — Lindau (see Gippel — Lindau a disease), Klippel's syndrome —

Trenone (see Blood vessels, malformations), Albright's syndrome (see Psevdogipopar an athyreosis), Larsen's syndrome and malformations of c. N of page.

Symptomatic treatment. Apply anticonvulsant, dehydrating agents. In rare instances carry out operational removal of tumorous educations in ts.n.s. and radiation therapy.

Forecast adverse. Patients perish at the epileptic status, from hypostasis and swelling of a brain (see). Quite often lead the T complicating a current to death of patients. page inf. diseases. Life expectancy of most of patients no more than 20 years.

Prevention consists in medicogenetic consultation

(cm). at a cut the failure from a child-bearing in families with the registered cases of T can be recommended. page

See also Fakomatoza.

Bibliography: Kalinin L. V. and a mustache e in E. I. Hereditary diseases of metabolism and a fakomatoza with defeat of a nervous system, M., 1981; The Kitchen garden -

L. S's nikova. To a question of an origin of a tuberous sclerosis, Zhurn. neuropath. and psikhiat., t. 65, No. 7, page 1004, 1965; Poyemny F. A., Ignatyeva E. N and Dadykina V. I. To a pathogeny of a tuberous sclerosis, in the same place, t. 73, No. 6, page 840, 1973; Bourne-ville D. - M& of Contribution l ’6tude de 1’idiotie, idiotie et ^pilepsie h^miplegi-que, Arch. Neurol. (Paris), t. 1, p. 81, 1880; Gritchley M. Earl C.J.C. Tuberose sclerosis and allied conditions, Brain, v. 55, p. 311, 1932; van der H o e v e T. Eye diseases in tuberous sclerosis of the brain and in Recklinghau-sen’disease, Trans, ophthal. Soc. U. K., v. 43, p. 534, 1923; Penrose L. S. A clinical and genetic study of 1280 cases of mental defect, L., 1938; Tuberous sclerosis, ed. by M. R. Gomez, N. Y., 1979;

Ross A. T. a. Dickerson W. W. Tuberous sclerosis, Arch. Neurol. Psychiat. (Chic.), v. 50, p. 233, 1943; Stefans-son K. Wollmann R. Distribution of the neuronal specific protein, 14 — 3 — 2, in central nervous system lesions of tuberous sclerosis, Acta neuropath., v. 53, p. 113, 1981.

L. V. Kalinina; V. A. Morgunov (stalemate. An.).