Brain injury (coma, acute period)

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 participate immediately in restoring 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.

Cell transplantation therapy in reanimating severely head-injured patients

Severe head injury remains one of main reason for mortality and disability among able-bodied persons. Outcomes of treating head-injured patients are largely defined within acute period of disease. In this period medical interventions are aimed at preventing the injury-triggered, second pathological processes that result in additional damages of brain tissues and are frequently associated with life-threatening consequences. Clinical effects of neuroprotective drugs in acute brain-injured patients are often unclear and doubtful, and there is an apparent necessity to search new approaches to recovery of life-saved, neurological functions.

Cell-based technologies allow to repair affected organs at a cellular level and, thereby, open up fundamentally new opportunities in the treatment for many severe diseases, including neurological ones. The central nervous system (CNS) is an "immune-privileged" organ where there are substantial barriers to the development of alloantigen-induced, immune processes. In fact, the grafted neural cells have been convincingly documented to be able to survive in the major histocompatibility complex (MHC)- incompatible CNS for a long period of time. There is also ample evidence from various experimental studies indicating abilities of the transplanted cells to proliferate and elaborate cell growth factors in brain lesions and to intensify markedly, thereby, brain tissue reparation processes.

A total of 38 severely head-injured patients were entered onto the controlled, retrospective clinical investigation. The patients initially were in state of coma (Glasgow coma scale score 3-to-7) owing to their traumatic brain injuries. Cell transplantation treatment was undertaken when consciousness of a patient did not exhibit signs of its recovering as long as at 5-to-8 week post-injury, and when there was a high risk of developing his long-term vegetative status and lethal outcome.

The cells prepared from fetal nervous and hematopoietic tissues were grafted subarachnoidally via a lumbar puncture. Twenty- five patients were cell-grafted once. Other 12, and 1 patients were cell-grafted twice, and thrice, respectively, at an interval of 10-to-14 days.

The control group consisted of 38 patients and was clinically comparable with the trial one.

The cell transplantation treatment was found to promote both wakening consciousness of the patients and their following neurological rehabilitation. As can be seen in Table 1, a death-rate in the trial and control group was 5% (2 cases) and 45% (17 cases), respectively. According to a Glasgow scale, favorable (good + satisfactory) outcomes of a disease were noted in 33 (87%) cell-grafted and only in 15 (39%) control patients.

Table 1. Outcomes of treating a severe brain injury.

Outcome	Trial (n=38)	Control (n=38)
Lethal	2 (5%)	17(45%)
Unsatisfactory	3 (8%)	6 (16%)
Satisfactory	15 (40%)	15 (39%)
Good	18 (47%)	0 (0%)

Statistical analysis revealed that the cell transplantation therapy generally improved the outcomes by 2.5-fold (see Figure 1).

Figure 1. The outcome values (M+m ) for the trial and control patients. For analysis, it was accepted that a lethal, unsatisfactory, satisfactory, and good outcome was coincided with 0, 1, 2, and 3 points, respectively.

No serious complications of the cell transplantation therapy were noted. The results point out advisability of applying such therapy in severely head-injured patients as early as within acute period of a disease. This therapy appears to be capable of preventing (inhibiting) the development of the second pathological processes which result in additional CNS damages and may lead to lethal outcome.

The examples of applying cell transplantation for acute brain injury are described below.

A 18 year-old female patient D was injured in a vehicular accident. On admission her pulse rate was 120-to 128 bpm, arterial blood pressure 100/60; there was psychomotor excitation, hyperhidrosis, and hyperthermia (up to 40º ?); the depressed fracture of temporal was seen on the right. Because of inefficiency of self-dependent respiration, the patient was transferred on artificial pulmonary ventilation. Her GCS score was 4. On MRI a subdural hematoma was revealed on the left; cisterns and ventricles of the brain were not visualized. The hematoma was removed in a surgery way. Intensive therapy enabled the patient to normalize her vital functions including respiration. However, in spite of all medical interventions undertaken, patient’s consciousness was not recovered. For this reason, the patient was cell-grafted on 37 and 48 day postinjury. Signs of awakening patients’s consciousness appeared as early as at 4 day after the first CT. At 7 days after the second CT the consciousness was recovered to a level of light obnubilation. Three months later completed recovery of her psychical functions was noted . As early as at 6 month after CT treatment, MRI signs of her brain atrophy almost completely disappeared (see Figure 2 A,B). The Glasgow outcome of her disease was good. At 1.5 year post-injury she became a student of the university faculty. By the time of preparing this manuscript, she was an excellent student in her third year.

Figure 2. MRI scans of patient D before (A) and at 6 months after CT therapy (B). For description see text.

A 24-year-old male patient B was admitted to the Emergency City Hospital after a vehicular accident. On admission his pulse rate was 110 bpm, arterial blood pressure 150/90; respiration was superficial, arrhythmical, at 28/min; there was psychomotor excitation with periodic hormetonic convulsions. His GCS score was 5. The patient was transferred on artificial pulmonary ventilation. MRI revealed an intracranial hematoma in the right temporoparietal area. This hematoma (120 ??) was removed in a surgery way. Intensive therapy enabled the patient to restore adequate self-dependent respiration on 5 day after trauma. Repeated MRI revealed contusion focuses of III type in frontotemporal-basilar brain areas. In spite of conducting intensive rehabilitation therapy, the patient did not recover his consciousness over 28 days. The patient was cell-grafted twice on 28 and 40 day post-injury. Recovery of patient’s consciousness to a level of light obnubilation occurred as early as on 6 day after the last CT. Appearance of his directional sense was noted 5 days later, whereas recovery of his time sense took significantly more time. The patient was discharged on 52 day post-injury. The Glasgow outcome of his disease was good. Three years later he became a student of the university faculty, successfully managing his educational task.

For more information see the publications.