Cerebral palsy

Treatment.

Immature (stem) cells are implanted into the subarachnoid space of a patient via a lumbar puncture ( patent of RF ¹ 2233665). The grafted cells release a variety of axonal growth-stimulating, neurotrophic factors, but also participate immediately in restoring affected nervous communications.

A patient firstly undergoes two cell transplantations at an interval of 10-to-14 days. The further treatment regimen is determined depend on the changes in neurological status of the patient.

The treatment is conducted in the neurosurgical department.

Infectious safety.

The donor material is subjected to 3-level testing for infection (2 immunoenzyme analyses and 1 PCR examination).

Side effects.

A rise in temperature until 390, meningisms, nausea and vomiting are possible during first 2 days after a cell transplantation procedure. Those effects are reduced by the appropriate drug therapy. No long-term complications are registered.

Clinical effect.

The long-term stimulation of both reparative and functional brain activity by grafted cells is capable of providing material neurological improvements in the recipient.

STEM CELL TRANSPLANTATION FOR INFANTILE CEREBRAL PALSY (CP)

Infantile cerebral palsy (CP) is a disease due to brain injury occurring at the stage of active brain development. Children with severe forms of CP are handicapped persons from birth. The standard treatment of CP patients is hugely complex and includes physical rehabilitation, as well as drug therapy aimed to both reducing muscular spasticity and improving brain functionality. Such cure has only very limited success, because it has no significant effect on reparative activity of the affected brain tissues.

The stem cell transplantation therapy aimed directly to augmenting reparative abilities of an injured brain, opens new opportunities in treating CP. By experimental and clinical investigations it is established firmly that when grafted into the injured brain, immature (stem) cells are able to ameliorate greatly injury-caused, neurological defects.

By present 125 severely brain-injured CP patients have been subjected to stem cell transplantation therapy. Immature (stem) cells were grafted subarachnoidally via a lumbar puncture. Each patient underwent 2 or 3 cell graftings at various time intervals. According to the available data, apparent neurological improvements are being developed in the majority (85%) of cell-grafted CP patients.

For comparable analysis of treatment outcomes, the controlled investigation with 30 stem cell-treated CP patients has been conducted. The indications for cell-based therapy were a severity of disease and a poor prognosis of its course, but also the lack of appreciable benefits from standard therapy as long as during 1-to-2 years. The control group was composed of 30 CP patients, who have undergone quality conventional interventions including medicamentous one. The trial and control groups were carefully balanced by both clinical and prognostic parameters (see Table 1 )

Table 1. Patients’ characteristics.

CHARACTERISTIC TRIAL CONTROL
Number
Male
Female
Average age
Double hemiplegia
Spastic diplegia
Atonia– astatia

Level of functional activity (Ì+ m)
 30
19
11
3.1
26
2
2


14 ± 2 		30
18
12
3.2
26
2
2


14 ± 3

Thirty trial patients received 73 cell graftings in all (1, 15 and 14 patients were cell-grafted 1, 2 and 3 times, respectively). Motor and mental faculties of each of patients were evaluated at 1 year after stem cell transplantation therapy.

With cell-based therapy, apparent clinical improvements were noted in 28 of 30 patients. The overall functional activity of the trial patients was increased by 65 points and reliably exceeded the corresponding control value (see Figure 1). The level of self-servicing CT-treated patients exceeded the control one 6.5-fold (see Figure 2). These results mean that enhancing the functional activity of a control patient was commonly not sufficient to render him less dependent upon outside assistance.

With cell-based therapy, 21 out of 24 patients initially unable to retain independently head in vertical position became able to consistently execute this function. In the control group only 6 out of 28 patients recovered this function in full measure. All both trial and control patients initially failed to hold toy by hand. Finally, 27 trial and only 4 control patients became able to execute independently this function. With cell-based therapy, 20 out of 29 patients initially incapable of crawling on abdomen became able to execute this function. None of 30 control patients achieved such result. Initially, 29 trial and all 30 control patients failed to sit. Finally, 17 trial and only 5 control patients could sit without assistance. A total of 29 trial patients and all 30 control ones initially failed to stand. Finally, 10 CT-treated and none control patients could stand without support. With cell-based therapy 6 out of 29 patients initially incapable of walking became to walk sufficiently without any help. None of 30 control patients achieved such result.

Figure 1. Activity of primary psychomotor functions of patients before and 1 year after treatment

Figure 1. Activity of primary psychomotor functions of patients before and 1 year after treatment

evel of self-servicing of patients before and 1 year after treatment.

Figure 2. Level of self-servicing of patients before and 1 year after treatment.

Finally, 23 out of 27 trial and 3 out of 28 control patients became capable of tracking toy by eyes. Understanding the addressed speech was developed in 18 out of 23 trial patients and 8 out of 26 control ones. Appearance of a meaning-bearing speech was noted in 17 out of 30 trial patients and only 1 out of 30 control ones.

With cell-based treatment, 8 out of 18 trial patients having initially a convergent cross-eye of central genesis, ameliorated this defect. Of 4 patients with an episyndrome 3 ones became much less dependent on taking anticonvulsants .

The development of neurological improvements strongly correlated with positive changes in eye grounds. The majority of evaluable patients initially had a hypertonic retinal angiopathy. With cell-based therapy, the patients exhibited normalization of their eye grounds, indicating improvements in their brain blood flows.

No reversion of clinical effects of stem cell-based therapy was observed. This therapy appears to be safe and well tolerated. No serious complications related to functionality of the grafted cells were noted.

Collectively, the results suggest that stem cell-based therapy may be highly effective in treatment of CP patients who are refractory to standard medicamentous interventions. Ten cases of applying CT therapy are described below.

A 3 year- old male patient P with double hemiplegia (a history ¹ 368) was from the first pregnancy complicated by toxiñosis with danger of fetus wastage. The child came into the world at 36 weeks, as a result of Cesarean section. The newborn child had a weight of 1600g and a height of 44 sm. At 6 months of age he has been ill with double-sided pneumonia.

On admission the patient was incapable of turning from abdomen to back, holding toy by his hand, sitting, standing, walking, tracking toy by eyes, speaking, and understanding addressed speech, while he was able to make attempts to retain his head in vertical position. Epileptic seizures until 20 times per a day were noted. The activity of his primary psychomotor functions was assessed by 5 points, the level of his self-servicing was 0 %.

The treatment included 3 stem cell transplantations at 2 month intervals.

One year later the patient could turn from abdomen to back, hold toy by hands, sit, stand, walk with support, track toy by eyes, understand addressed speech, enunciate several words; and retain his head in vertical position. His epileptic seizures occurred until 2 times per a day. The activity of his primary psychomotor functions was assessed by 85 points, the level of his self-servicing was 70%

A 5 year- old female patient A with double hemiplegia (a history ¹ 824) was from the 9th pregnancy complicated by prenatal infection and toxiñosis with danger of fetus wastage. The childbirth was the third, premature at 32 weeks; the child had a weight of 1770 g and a height of 45 sm.

On admission the patient was able to make attempts to track toy by eyes. All her remaining evaluable functions were profoundly defective. The activity of her primary psychomotor functions was assessed by 5 points, the level of her self-servicing was 0 %.

The treatment included 3 stem cell transplantations at 2 month intervals.

One year later the patient sat, stood, and walked, all with support; and executed independently each of the remaining valuable functions. One epileptic seizure was usually registered within a day. The activity of her primary psychomotor functions was assessed by 85 points, the level of her self-servicing was 70%

A 3 year- old male patient S with double hemiplegia ( a history ¹3024) was from the 7th pregnancy (the second childbirth) complicated by congenital toxoplasmosis and pneumonia. The child came into the world as a result of Cesarean section. The newborn child had a weight of 3400 g and a height of 51 sm..

On admission the patient could make attempts to track a toy by eyes, and was unable to execute each of the all remaining valuable functions. The activity of his primary psychomotor functions was assessed by 5 points, the level of his self-servicing was 0 %.

The treatment included 3 stem cell transplantations at 2 month intervals.

One year later the patient could stand without support. He was able to sit and to walk with support. The patient could make attempts to turn from abdomen to back. Each of all the remaining valuable functions was executed by the patient without outside assistance. The activity of his primary psychomotor functions was assessed by 80 points, the level of her self-servicing was 60%

A 1.5 year- old female patient P with double hemiplegia (a history ¹ 1455) was from the first pregnancy with danger of fetus wastage. Childbirth was at 36 weeks; the newborn child had a weight of 3000 g. She has been ill with double-sided pneumonia. A heart disease was diagnosed, due to a defect of an interventricular septum

On admission the patient could make attempts to retain his head in vertical position. All her remaining valuable functions were profoundly defective. Epileptic seizures until 10 times per a day were noted. The activity of her primary psychomotor functions was assessed by 5 points, the level of her self-servicing was 0 %.

The treatment included 3 stem cell transplantations at 1 month intervals.

One year later the patient could walk with support and make attempts to turn from abdomen to back. All the remaining valuable functions were executed by her independently. The activity of her primary psychomotor functions was assessed by 90 points, the level of her self-servicing was 80%

. A 5 year- old female patient K with double hemiplegia ( a history ¹ 3255) was born from the first pregnancy complicated with toxiñosis and danger of fetus wastage. Childbirth was premature. The newborn child had a weight of 2700g.

On admission the patient was able to retain head, to stand and walk with support. She executed none of the remaining valuable functions. The activity of her primary psychomotor functions was assessed by 20 points, the level of her self-servicing was 10 %.

The treatment included 2 stem cell transplantations at a 1 month interval.

One year later the patient could make attempts to turn from abdomen to back, hardly understood addressed speech and was able to enunciate several words She executed each of the all remaining valuable functions without outside assistance The activity of her primary psychomotor functions was assessed by 85 points, the level of her self-servicing was 70%

A 3 year- old male patient L with double hemiplegia ( a history ¹ 3254) was from the first pregnancy. The anamnesis of the patient was unknown in detail because he was brought up by his grandmother

On admission the patient was able to track toy by eyes, to understand addressed speech, but also to make attempts to retain head in vertical position. He enunciated several words. All his remaining valuable functions were profoundly defective. The activity of his primary psychomotor functions was assessed by 25 points, the level of his self-servicing was 10 %.

The treatment included 2 stem cell transplantations at a 5 month interval.

One year after the patient was able to walk with support and execute each of remaining valuable functions without outside assistance The activity of his primary psychomotor functions was assessed by 95 points, the level of his self-servicing was 90%

A 5 year- old female patient M with spastic diplegia ( a history ¹ 1659) was from the first pregnancy . Childbirth was at 30 weeks; the newborn child had a weight of 1400 g. She was at a reanimation department for 1 month after her birth.

On admission the patient was able to retain head in vertical position, to hold toy by hand, and to understand addressed speech. All her remaining valuable functions were profoundly defective. The activity of her primary psychomotor functions was assessed by 25 points, the level of her self-servicing was 20%.

The treatment included 2 stem cell transplantations at a 2 month interval.

One year later the patient was able to execute each of all valuable functions without outside assistance. The activity of her primary psychomotor functions was assessed by 100 points, the level of her self-servicing was 100 %.

A 4 year- old female patient G with double hemiplegia ( a history ¹ 3011 ) was from the fiveth pregnancy (the second childbirth). The child was born at 36 weeks with a weight of 2000 g. She was at a reanimation department for 5 days after her birth.

On admission the patient was able to retain head in vertical position, to sit with support, to track toy by eyes, to understand addressed speech and to speak, but also to make attempts to hold toy by hand. All her other valuable functions were profoundly defective. The activity of her primary psychomotor functions was assessed by 40 points, the level of her self-servicing was 30 %

The treatment included 2 stem cell transplantations at a 1 month interval.

One year later the patient was able to execute each of all valuable functions without outside assistance. The activity of her primary psychomotor functions was assessed by 100 points, the level of her self-servicing was 100 %

A 3 year- old male patient G with double hemiplegia (a history ¹ 3832) was from the first pregnancy with a weight of 3200 g. He was at the reanimation department for 1 month after his birth .

On admission the patient understood hardly addressed speech and was able to make attempts to retain his head in vertical position. All his other valuable functions were profoundly defective. The activity of his primary psychomotor functions was assessed by 10 points, the level of his self-servicing was 0 %

The treatment included 2 stem cell transplantations at a 2 month interval.

One year later the patient could sit, stand and walk, all with support. He was able to execute each of the remaining valuable functions without outside assistance. The activity of his primary psychomotor functions was assessed by 85 points, the level of his self-servicing was 70 %

A 2-year-old male patient M with double hemiplegia (a history ¹ 3832) was from the third pregnancy (the third childbirth). The child was born at 35 weeks with a weight of 2300g and a height of 46 sm. An intraventricular hemorrhage was noted.

On admission the patient executed none of the valuable functions. The activity of his primary psychomotor functions was assessed by 0 points, the level of his self-servicing was 0%.

The treatment included 2 stem cell transplantations with a 1 month interval.

One year later the patient was able to retain his head, to hold toy by hands and to turn from abdomen to back. He understood addressed speech and enunciated several words. The patient made attempts to crawl, to sit and to stand. The activity of his primary psychomotor functions was assessed by 75 points, the level of his self-servicing was 40%.

For more information see the publications.

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