Infantile cerebral palsy

Immature (stem) cells are implanted into a subarachnoid space of a patient via a lumbar puncture. The treatment is conducted in the neurosurgical department.

The grafted cells release a variety of axonal growth-stimulating, neurotrophic factors, but also, be themselves” are implicated in restoring the affected nervous communications.

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

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.

Stem cell transplantation for infantile cerebral palsy (cp)

Infantile cerebral palsy is a disease due to brain injury occurring at the stage of active brain development. Children with severe forms of cerebral palsy are handicapped persons from birth. The standard treatment of cerebral palsy patients is hugely complex and includes physical rehabilitation, as well as drug therapy aimed to both reducing muscular spasticity and improving brain functionality. Such a cure has only very limited success, because it has no significant effect on the reparative activity of the affected brain tissues. The stem cell transplantation therapy, aimed directly to augment regenerative abilities of an injured brain, opens new opportunities in treatment for cerebral palsy. The grafted, stem cells have been firmly established to be capable of ameliorating greatly injury-caused, neurological defects.

In CICT 125 severely brain-injured, cerebral palsy patients have been subjected to stem cell transplantation therapy. 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, cerebral palsy patients.

For comparable analysis of treatment outcomes, the controlled investigation with 30 stem cell-treated, cerebral palsy patients has been performed. The indications for the 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 cerebral palsy 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	Trail	Control
Number	30	30
Male	19	18
Female	11	12
Average age	3.1	3.2
Double hemiplegia	26	26
Spastic diplegia	2	2
Atonia-astatia	2	2
Level of functional activity (M±m)	14 ± 2	14 ± 3

Motor and mental faculties of patients were evaluated accordingly the special 100 point scale assessing 7 motor and 3 mental functions (see table 2), which are traditionally examined in neurological practice. The complete (independent) execution and the incomplete execution of each function was assessed by 10 and 5 points, respectively, whereas the failure to execute by to 0 points. Execution of a function was considered as incomplete when a patient made attempts to its accomplishment, not reaching for the desired result. An independent (complete) execution of each of all 10 valuable functions renders a patient able to service himself in full measure. An incomplete execution of any function does not expand really functional abilities of a patient. Therefore, on examining capacity of a patient to service himself, an incomplete execution was assessed by 0 points.

Table 2. A 100 point scale for assessing 10 primary psychomotor functions of a cerebral palsy patient.

N	Function	Failure to execute (%)	Incomplete (doubtful) execution (%)	Complete execution (%)
1	Retention of the head	0	5	10
2	Turning from the abdomen to the back	0	5	10
3	Taking toy by the hand	0	5	10
4	Crawling on the abdomen	0	5	10
5	Sitting	0	5	10
6	Standing	0	5	10
7	Walking	0	5	10
8	Tracking the toy by eyes	0	5	10
9	Understanding the addressed speech	0	5	10
10	Speaking	0	5	10

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 the stem cell transplantation therapy.

Apparent clinical improvements were noted in 28 of cell-grafted 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 of the trial patients exceeded that of the control patients 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.

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

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

With the cell-based therapy, 21 out of 24 patients initially unable to retain independently head in vertical position became able to consistently execute this function. Only 6 out of 28 control 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 the 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 trial and none of control patients could stand without support. With the 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.

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 the 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 the cell-based therapy, these 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 cerebral palsy patients who are refractory to standard medicamentous interventions.

The examples of applying the cell transplantation therapy for cerebral palsy are described below.

A 3 year- old male patient P with double hemiplegia (a history ? 368) was from the first pregnancy complicated by toxi?osis 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 ? 824) was from the 9th pregnancy complicated by prenatal infection and toxi?osis 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 ?3024) 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 ? 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 ? 3255) was born from the first pregnancy complicated with toxi?osis 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 ? 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 ? 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 ? 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 ? 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 ? 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.