RU2233665C2 - Agent for treatment of infantile spinal paralysis - Google Patents

Abstract

FIELD: medicine, neurosurgery, neurology, pediatrics.

SUBSTANCE: invention proposes an agent for treatment of infantile spinal paralysis that represents the suspension of cells mixture of fetal (gestation is 16-22 weeks) nervous and hemopoietic liver tissue taken in their ratio = (5-15):1. Invention provides carrying out treatment of child more early significantly (in age beginning since 1 month of life) and as soon as after diagnosis of infantile spinal paralysis. Transplantation of the claimed agent can promote to early development and stable recovery of psychic functions being agent is administrated into spinal cord that simplified and reduces traumaticity of its application.

EFFECT: enhanced effectiveness of treatment, valuable medicinal properties of agent.

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Description

The invention relates to medicine and can be used in neurosurgery, neurology, pediatrics.

Known tool for the treatment of cerebral palsy (cerebral palsy), which is a device - "Travistat" (Semenova KA Reconstructive treatment of patients with the residual stage of cerebral palsy. - M., Antidor, 1999). With its help, dynamic proprioceptive correction of cerebral palsy is carried out (EG Sologubov, System for the rehabilitation of patients with cerebral palsy by the method of dynamic functional proprioceptive correction: Thesis for the degree of doctor of medical sciences - Moscow, 1997). Correction of pathological settings of the trunk and limbs of the patient leads to the emergence of a powerful proprioceptive afferent flow that carries information about the normalized position of the body in space.

However, this remedy cannot be considered pathogenetically justified, because the impact is only on one of the manifestations of a brain disease - muscle spasticity, and not on a pathologically altered brain, and it completely does not solve the issue of restoring mental function. In addition, the use of expensive bulky costumes, the effect of which is limited by the time of direct exposure, is required. Gravistat is used in children older than 7 years.

Known drug “Botox” (“Botox”), which is used in the treatment of cerebral palsy in order to reduce muscle tone involved in the construction of a pathological motor stereotype in patients with spastic forms of cerebral palsy (Cosgrove AP The use of botulinum toxin in cerebral palsy // Eur. J. Neurol . 1995. Vol. 5. P.302-321). A similar effect is achieved with chronic intrathecal administration of the drug "Baclofen" (Cosgrove A.P. The use of botulism toxin in cerebral palsy // Eur. J. Neurol. 1995. Vol. 5. P.302-321). The drugs are administered by round-the-clock titration using special equipment mounted on the child. The use of these drugs is time-consuming, requires complex equipment, is dangerous due to the possibility of complete relaxation of all muscle groups and respiratory failure. At the same time, the effect of the administration of these drugs is short-term, lasts on average 3-4 months, after which the spasticity phenomena recur and a repeat injection is required. Both of these drugs do not affect the psycho-emotional state of the patient. Botox and baclofen are not used in children of the first year of life.

Closest to the claimed invention is a tool for the treatment of cerebral palsy, which is an embryonic tissue of the brain in the form of pieces of 2-3 cubic meters. mm, which are laid intraparenchymally in the cerebral cortex, in the zones of the most pronounced atrophy (Tsimbalyuk V.I., Pichkur L.N., Martynyuk V.Yu. Neurotransplantation in the treatment of the consequences of the apallic syndrome / In the book: First Congress of Neurosurgeons of the Russian Federation ( June 14-17, 1995): abstracts - Ekaterinburg, 1995, pp. 317-318). This tool allows you to improve motor function, but does not allow to achieve improvement in mental activity. In addition, for the transplantation of pieces of tissue, trepanation of the skull and encephalotomy, i.e. cause additional brain injury, which, in turn, may worsen its condition. The latter circumstance practically excludes the possibility of repeated transplant administrations and thereby increase the clinical effect.

The funds listed, therefore, cannot be considered sufficiently effective in the treatment of cerebral palsy.

SUMMARY OF THE INVENTION

A treatment for cerebral palsy is proposed, which is a mixture of fetal cells (gestational age 16-22 weeks) of nervous and hematopoietic liver tissue. The tool is proposed to use in the form of a cell suspension.

The suspension contains cells of the nervous and hematopoietic liver tissue in the ratio (5-15): 1. The total number of cells in the administered dose corresponds to (1.0-1.5) × 10 ⁸ cells. The mixture is administered subarachnoidly into the spinal cord.

It is known the use of a neurotransplant of this composition for the treatment of traumatic coma (Patent No. 2160113 dated 10.12.2000), however, its use for the treatment of cerebral palsy is not known from the prior art.

The use of the invention allows

1. To treat the child much earlier (at the age of 1 month), immediately after the diagnosis of cerebral palsy. Transplantation of the claimed drug can contribute to the early development and stable restoration of mental functions, as well as prevent the harmful effects of prolonged inactive state of the affected parts of the brain.

2. To carry out repeated transplantations over several months, increasing the result, and thus obtain a stable effect of partial or full compensation of impaired functions.

3. Significantly improve not only the motor, but also the psycho-emotional sphere of activity of the child.

4. To reduce the financial costs of parents and the state for the rehabilitation of children with cerebral palsy.

5. Since the claimed tool is intended for administration (and can be introduced, unlike the prototype) not in the brain, but in the spinal cord, this, on the one hand, greatly simplifies its use, and on the other hand, significantly reduces the morbidity associated with using the product.

The invention is as follows.

The patient is examined: electroencephalography (EEG), neuroelectromyography (EMG), transcranial ultrasound dopplerography, X-ray computed tomography or magnetic resonance imaging (MRI) of the brain. If the absence of signs of brain compression and the presence of an atrophic process, a decrease in the electrical activity of the brain due to uncoupling of the cortical-subcortical relationships, and a decrease in the rate of cerebral blood flow are confirmed instrumentally, a subarachnoid injection of a suspension of immature cells is performed.

In the patient’s position on the side in the interval between the spinous processes of the L3-L4 vertebrae, a subarachnoid space is punctured. 5 ml of cerebrospinal fluid is removed, for example, and, for example, 5 ml of a suspension of a cell suspension including (1.0-1.5) × 10 ⁸ fetal cells (gestation period 16-22 weeks) of nerve and hematopoietic tissue is injected through a syringe ratio (5-15): 1, whose viability is at least 90%. After such an introduction, the patient is placed in a ward, where his mental, neurological and therapeutic status is monitored by examining, measuring pulse, blood pressure and body temperature. With the development of a pyrogenic reaction, it is stopped within 2-3 hours with antipyretics. 14 and 28 days after the first transplant, a second and third transplant is performed. Over the next 3 years, somatic and neuropsychiatric status, magnetic resonance imaging, electroencephalography, and transcranial ultrasound dopplerography are monitored annually.

Information confirming the possibility of carrying out the invention with the implementation of the appointment.

Example 1. Patient Ch., 2 years 1 month. He was admitted to the pediatric neurosurgery clinic on August 5, 1999. Diagnosis: cerebral palsy, double hemiplegia. Before entering the clinic for 2 years, the child was systematically treated with medication and physiotherapeutic methods in a specialized center. The treatment effect was minimal. On admission it was noted: the child is aggressive, negative, does not come into contact with medical personnel, it is also difficult to communicate with his parents — he does not understand the addressed speech; converging strabismus, the child does not fix the gaze, the pharyngeal reflex is reduced; decrease in the strength of the upper and lower extremities to 1 point on both sides; increased tone of all muscle groups to 5 points; tendon reflexes are sharply animated, clonus of the feet, Babinsky's bilateral symptom; the child does not sit, does not walk, relies on tiptoes with a cross in the lower extremities; on MRI, pronounced atrophic open communicating external and internal hydrocephalus. An instrumental examination also showed a decrease in the electrical activity of the brain and the speed of cerebral blood flow through the arteries of the circle of the Wellis. According to EMG, there was a bilateral suprasegmental lesion for all limbs.

The patient is thrice, in August, October and November 1999. 5 ml of cell suspension were transplanted, including 1 × 10 ⁸ fetal cells (gestation period 16-22 weeks) of nerve and hematopoietic liver tissue in a ratio of 10: 1. After the first transplantation, positive dynamics were noted - the child became calmer, more contact with parents, however, aggression remained with respect to medical personnel, other children. After the second transplant, muscle tone decreased to 2 points, interest in games appeared. 6 months after the third transplantation, the child became more contact with medical personnel and other children, aggressiveness and negativity disappeared, interest in games remains. Muscle strength increased to 4 points. The child began to sit, understand the speech addressed to him and utter individual words. Pupillary motor disorders disappeared. During 3 years of observation, the restored functions were stably preserved.

Example No. 2. M., 3 years old. Was admitted to the clinic of pediatric neurosurgery on May 7, 2000. Diagnosis: cerebral palsy, spastic diplegia. For 2.5 years she was treated in a specialized children's neuropsychiatric dispensary using traditional methods. It was possible to maintain normal mental development, but practically no shifts were achieved in the motor function of the lower extremities. Upon admission to the clinic, it was noted that the child is intellectually developed according to age, understands conversations, speaks, has good contact with staff and parents. Neurological status: convergent strabismus, strength in the hands of 5 points, in the legs 1 point, tone in the hands is normal, in the legs increased to 5 points; the child crawls with the help of the upper limbs, resting on legs on tiptoe, with a cross of legs. EEG showed a moderate decrease in the bioelectrical activity of the brain against the background of age-related features of the formation of cortical rhythm. When EMG revealed suprasegmental lesions for the lower extremities. MRI revealed a moderate open communicating hydrocephalus. Twice, in May, and then in June, transplantation of fetal cells was performed. 5 ml of cell suspension was transplanted, including 0.9 × 10 ⁸ fetal cells (gestational age 16-22 weeks) of nerve and hematopoietic liver tissue in a ratio of 12: 1.

Within 1 month after the first transplantation, the child began to walk with support. After the second transplant, after 3 months, the strength in the lower extremities increased to 3 points, and the tone decreased to 1 point. The girl began to walk on her own. Strength in the lower extremities increased to 4 points. Strabismus decreased. Rapid psycho-emotional development of the child was noted. MRI revealed no pathology. When EEG marked age-related features of the formation of cortical rhythm. The positive therapeutic effect persisted throughout the observation period - 2 years.

Claims (1)

An agent for the treatment of cerebral palsy, which is a suspension of a mixture of cells of fetal nervous and hematopoietic liver tissue with a ratio of (5-15): 1.