Tuberozny sclerosis — the gene disease which is characterized by defeat of nervous system in the form of epilepsy and mental retardation, polymorphic skin symptoms, tumoral and not tumoral processes in somatic bodies. The diagnostic algorithm consists of inspection of nervous system (MPT, KT of a brain, EEG), an ophthalmologic research, inspection of internals (ultrasonography, MRT of heart, KT of kidneys, a X-ray analysis of lungs, a rektoromanoskopiya). The main directions of treatment are: antiepileptic therapy, neuropsychological correction, observation and timely surgical treatment of new growths.
The Tuberozny Sclerosis (TS) — the hereditary neyroektodermalny pathology which is shown changes of skin, epileptic attacks, an oligofreniya (intellectual backwardness) and emergence of new growths of various localization. Along with a neurofibromatosis, Gippelya-Lindau's disease, Louis Bar syndrome, Sterdzha-Weber's disease, etc., the CU treats fakomatoza. Incidence makes 1 case on 30 thousand population, among newborns — 1 case on 6-10 thousand. Not only family, but also sporadic cases are known. And the last make up to 70%.
For the first time the tuberozny sclerosis was described by Recklinghausen in 1862. Frenchman Burnevill in 1880 in detail investigated the morphological changes happening in a brain at this disease and for the first time used the term "tuberozny sclerosis". In 1890 the dermatologist Pringl made the description angiofibry persons at patients with the CU. Therefore in literature on neurology it is possible to meet the synonymous name of the CU — Burnevillya-Pringl's disease.
Reasons of a tuberozny sclerosis
The disease has the genetic nature. The majority of cases is caused by emergence of new mutations and only 30% autosomno-prepotent inheritance of the gene aberrations which are available for parents. Allocate a tuberozny sclerosis type 1 which development is caused by mutations in a gene 34 loci of the 9th chromosome, responsible for coding of a gamartin, and a tuberozny sclerosis type 2 connected with violations in the 13th site of the 16th chromosome which is responsible for coding of a tuberin.
Biochemical aspects of pathogenesis are up to the end not studied. It is known only that normal and are factors of suppression of tumoral growth. The expanded glial elements of cerebral fabric histologically presented by huge cages with atypically increased kernels and a large number of shoots act as a morphological substratum. Glial growths are formed by subependimalny knots, cortical tuber and specific islands in white substance. All these educations tend to calcification. Subependimalny knots often give rise to formation of a gigantokletochny astrotsitoma. In 10% of cases defeat of tissues of cerebellum is noted. Glial growths are observed also on a disk of an optic nerve and in peripheral departments of a retina.
Symptoms of a tuberozny sclerosis
The clinic which the tuberozny sclerosis has is very variable. It includes damage of the central nervous system (CNS), dermatological and ophthalmologic manifestations, new growths of internals. The debut falls on various age periods, but more often the tuberozny sclerosis demonstrates within the first 5 years of life. Current options, various on weight, are possible. In mild cases patients have a number of facultative nonspecific symptoms and often do not undergo diagnostics on existence of the CU. The Tuberozny sclerosis in the erased form proceeds without epipristup, mental retardation and disorders of behavior.
Defeat of TsNS
Changes in TsNS act as the dominating manifestations of the CU. The convulsive syndrome from which usually demonstrates a disease occurs among them most often (in 80-90% of cases). Infantile spasms (Vest's syndrome), then transformed to Lennox-Gasto's syndrome are characteristic of the episindrom debuting on the first year of life. Atypical absansa, somato-and sensomotorny paroxysms, secondary and generalized attacks are possible. Emergence aged about one year, the high frequency and heterogeneity of attacks are followed by their resistance to antikonvulsantny (antiepileptic) therapy. Epileptic paroxysms are the reason of a delay of mental development and violations of behavior (aggression, autism, SDVG) at children.
In half of cases the tuberozny sclerosis is followed by the oligofreniya expressed in various degree. Along with epilepsy, the reason of its development existence of cortical tuber is considered. Already at younger age at children the abnormal behavior is noted: the general concern, a capriciousness and discontent along with sluggishness, difficulties of a pereklyuchayemost of attention. Extent of these violations of subjects is higher, than earlier there was a tuberozny sclerosis. At most of patients sleep disorders are also observed. They are characterized by night awakenings, an insomniya, sleep-walking, early morning transition from a dream to wakefulness.
Changes from skin accompany a tuberozny sclerosis practically in 100% of cases. They are characterized by big polymorphism of elements and their combinations. Most often (in 90% of cases) hypopigmentation spots which arise usually in the first 3 years of life are observed and further increase the quantity. They are asymmetrically scattered on buttocks, a trunk and on the front and lateral surfaces of extremities. The depigmentation of eyelashes, eyebrows and hair is possible. In 14% of cases sites of a hyperpegmentation in the form of the spots more characteristic of a neurofibromatosis come to light. As a rule, them there are no more than 5 pieces.
Angiofibroma faces according to various data are noted at 50-90% of patients and are formed in the main ambassador of 4-year age. These are multiple or single dense small knots in the form of grains of millet, reddish or yellowish color. "The Magic Skin" takes place in 21–68% of cases. Usually arises during from 10 to 20 years. Represents the asymmetric sites of the rigid coarsened skin which are localized on a back and a waist, having the size from 2-3 mm to 10 cm. At Dermoscopy it is visible that shagreen sites consist of a set fibrous gamarty.
In 25% of cases the tuberozny sclerosis is followed by formation of fibrous plaques, in 30% of cases — soft dermatofibry. To 50% of patients after a puberty have okolonogtevy fibromas, inclined to progrediyentny growth. The last settle down on more often. Have an appearance of the dim red small knots or papules surrounding a nail plate.
Are noted seldom though almost at a half of patients of the CU existence gamarty an optic nerve and/or gamarty retinas comes to light. Gamartoma can have the flat smooth, slightly towering surface or represent knotty education, gamartoma of the mixed type — knotty in the center sometimes meet. The main manifestation gamarty is the progressing sight falling, but their subclinical current is often observed. Also other ophthalmologic frustration are possible: iris depigmentation, hypostasis of a disk of an optic nerve, kolobom, squint, angiofibroma century, cataract.
Damage of internals
The new growths of somatic bodies accompanying a tuberozny sclerosis differ in plurality and frequent bilateral defeat of pair bodies, is long subklinichesk proceed. The period of their demonstration fluctuates from 5 to 40 years. Treat the most patognomonichny new growths for the CU: rabdomioma of heart, cyst of lungs, kidneys, liver gamartoma, rectal polyps. In 4,5% of cases at the CU malignant tumors are observed, kidney and cellular cancer is more often.
From cardiovascular system heart tumors come to light. In 30-60% of cases it is rabdomioma. At their pre-natal development antenatalny death of a fruit can be observed. At a half of newborns with the CU rabdomioma come to light incidentally when performing EhoKG. At small children they are shown by arrhythmia, WPW syndrome, tachycardia, fibrillation of ventricles. The Intramuralny provision of a rabdomioma involves frustration of a sokratimost; the obturation the tumoral mass of heart cameras leads to heart failure. The senior children have rabdomioma mainly of a bessimptomna; blockade of a leg of a bunch of Gis, pseudo-ischemic deviations on the ECG is possible. Regress and even total disappearance of a rabdomioma to 6-year age is often observed.
Damage of lungs is noted at the patients having a tuberozny sclerosis after 30 years. On the roentgenogram the picture of "a cellular lung", characteristic of multiple pulmonary cysts, is defined. Damage of a GIT includes oral cavity tumors, defects of tooth enamel, multiple or single gamartoma in a liver, rectum polyps, not inclined to a malignization. Damage of kidneys accompany a tuberozny sclerosis in 50-85%. Angiomiolipoma, cysts, , can be noted, interstitsialny nephrite, glomerulonefrit. Pathology of kidneys acts as the reason of a lethal outcome, the second after defeat of TsNS, at the CU.
Diagnostics of a tuberozny sclerosis
It is possible to diagnose a tuberozny sclerosis only joint efforts of several experts (the neurologist, the ophthalmologist, the dermatologist, the cardiologist, the nephrologist) with carrying out broad hardware inspection of the patient. Cerebral epileptic activity is registered by means of EEG and EEG with tests. At children about one year carrying out a neyrosonografiya is possible. The greatest importance in diagnostics of defeats of TsNS have KT and MPT. Brain KT more informatively concerning calcific tuber and subependimalny knots, and brain MRT — in identification of not calcific tuber. For the purpose of timely diagnostics of an astrotsitoma passing of MRT or the KT-research at least time in 2 years is recommended to the children having a tuberozny sclerosis.
Comprehensive examination of somatic bodies is conducted: ECG, ultrasonography and MRT of heart, ultrasonography of an abdominal cavity, ultrasonography and KT of kidneys, urography, survey X-ray analysis of a thorax, rektoromanoskopiya, kolonoskopiya. Diagnostics of ophthalmologic defeats is performed by the direct and indirect oftalmoskopiya scanning retina tomographies.
Due to big polymorphism of the manifestations accompanying a tuberozny sclerosis, for establishment of the diagnosis use the diagnostic criteria developed in 1998 in Sweden. They include primary, secondary and tertiary signs. The Tuberozny sclerosis is reliable when 1 primary sign in combination with 2 secondary or tertiary takes place. The Tuberozny sclerosis is probable in the presence of 1 secondary and 1 tertiary or 3 tertiary signs.
Treatment of a tuberozny sclerosis
The fundamental direction in treatment of the CU is antikonvulsantny therapy as degree mental retardation and ZPR directly correlates with a frequency of epipristup, and the epileptic status can become the death reason. The choice of medicine depends on a type of paroxysms, at insufficient efficiency of monotherapy, the combined treatment is appointed. At Vest's syndrome apply and . Valproata act as medicines of the second turn. If the tuberozny sclerosis proceeds with partial epipristupa, then the combination of valproat to carbamazepine is considered basic therapy. In the absence of effect include in this scheme of treatment . At generalized epipristupa and partial paroxysms as monomedicine and in a combination with other antiepileptic means modern antikonvulsant and to levetiratseta can be applied.
Therapy mental retardation is carried out mainly by neuropsychological correction and comprehensive psychological support of the child. Purpose of nootrop and the other stimulating neuromedicines contraindicated because of existence of an episindrom. At identification of an astrotsitoma dynamic observation is made. Surgical removal of an intracerebral tumor is shown only at sharp increase in its sizes with rise in intra cranial pressure. Operation is performed by neurosurgeons.
Mainly waiting tactics is applied to new growths of somatic bodies. Surgical treatment is carried out according to indications, generally in cases when the tumor causes essential dysfunction of body or there is a threat of its malignant current.