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DMSO

Dimethy Sulfoxide Therapy in Severe Retardation in Down Syndrome Children

Part II

    Motor Area. In the control group the motor index varied according to chronological age, but maintained the same level during the time observed (the average before treatment was 56; after one year it was 58). In 10 cases out of 13 the motor index remained the same; in 1 it dropped, and it rose in 2. In the treated group, on the other hand, we observed a favorable increase, as at the beginning the average was 56, the same as that for the controls, but at the end of one year it was 72. Out of 15 cases, 8 improved more than 10 points, 1 dropped, and 6 remained the same.

    Adaptive Area. In the control group the initial average was 52, and at the final observation it was 49. In the treated group the initial average was 50, but it was 60 after the series of injections. Two-thirds of the cases increase more than 10 points, which indicated improvement in this aspect.

    Language Area. Control cases gave average of 56 and 54 before and afier observation respectively. Only 1 rose more than 10 points, and 6 dropped by that number. The treated group began with an average of 52 and ended with an average of 58; 4 rose more than 10 points, and 3 dropped that amount.

    Social Area. The control group gave an initial average of 45 and an average of 50 after one year. We must note that 4 of them rose more than 10 points and 9 showed no change. At the beginning of the observation the treated group gave an average of 40, which would be in accordance with the former group. At the end, however, they had increase to 64, a frankly favorable score; 10 rose more than 10 points, and only 2 dropped.

Figure 1. Results of a psychometric study of children between 3½ and 14 years of
age with trisomy-21 (13 controls and 15 treated with DMSO-amino acidtherapy).
The averages are according to the Binet-Kulman test. B= beforetreatment;
A= after treatment.

    We must note that in general, variation of individual figures was great. In both groups the character of the patients in general was quiet, but in some of those treated inquietude and at times intranquility were observed. Night sleep was generally deep. The mimetic capacity and expression improved noticeable in those treated; their environmental contact was also noteworthy. In the children over 3½ years of age the psychometric examination revealed the result shown in Figure 2.

Figure 2. Results of a phychometric study of children between 3½ and 14
years of age with trisomy-21 (11 controls and 16 treated with DMSO-amino
acid therapy). The averages are according to the Binet-Kulmantest. B= before
treatment; A= after treatment.

    Motor Area. The controls were stagnant, as the average motor index before treatment was 34, and it was 36 afier observation. Taking the cases individually, the same result was observed. In the treated group the initial average was 38, which is comparable to that of the controls. At the end of the therapy, however, the average score was 11 points over the former figure, at a value of 49. Taking the cases individually, 7 cases out of 16 rose 10 points, while the rest remained stationary.

    Language Area. The utilization and comprehension aspects of verbal communication were examined. The results were as follows: Regression was not observed in the control group, but stagnancy in both were as follows; Regression was not observed in the control group, but stagnancy in both aspects prevailed in alí control cases. The utilization average as initially 21, and it was 23 at the end of a year. In comprehension, the averages were 25 and 34 respectively. In the treated group, the averages for language utilization were 27 initially and 37 after one year. Of these cases, 6 improved more than 10 points and 7 remained stationary. In comprehension, the averages were 42 and 52; 6 out of 16 children improved, and the others stayed the same. The two aspects did not necessarily improve or worsen simultaneously; four cases were unbalanced in this sense. Only one dropped in utilization, and none dropped in comprehension.

    Graphic Age. No significant variation was seen in the control group, as the averages were 28 initially and 34 afier a year of observation. Out of the 11 studied, 2 showed rises of more than 10 points. At the beginning of treatment, the group treated with DM80 therapy had an average score of 24 points, which corresponded to that of the controls, whereas at the end it rose to 39, dernonstrating a favorable difference of 15 points. Specifically, 12 out of 16 showed an improvement of over 10 points, while the others remained stationary; none dropped.

Figure 3. Average inteligence quotients of children between 3½ and 14
years of age with trisomy-21 (11 controls and 16 treated with DMSO-amino
acid therapy). The averages are according to Gesill, Wieneland, and Binet.
B= before treatment; A= after treatment.

    Intelligence Quotient. The results are shown in Figure. The control group began the observation with an average of 34 and finished with an average of 33; all variations were of less than 5 points. The treated group began with an average of 29, very close to that of the controls, and ended with an average of 40; in other words they showed a significant improvement. The scores of 7 cases increase more than 10 points, and none dropped in score. The neurologic examination of the children under 3½ years of age was carried out according to the models already indicated; the results are shown in Figure 4.

Figure 4. Results of a neurological study of children under 3½ years of age with trisomy-21
(13 controls and 15 treated with DMSO-amino acid therapy), during 1 year of observation.

    Sense Organs. In both groups, the hearing of some of the patients was apparently diminished. In the older children, hearing was normal. In the control group there was a case of palpebral ptosis, which possibly partly obstructed the patient`s motor development. We have already mentioned the preexisting bilateral cataracts and squint in the treated group. We must note that the child with congenital blindness showed deficient evolution in nearly alí the parameters; after surgical operation he improved moderately in relation to his previous period.

    Reflexes. We will only say that the control group appeared to have weaker reflexes, but none had important alterations.

    Statics. In the control group, 7 out of 13 were classified as deficient, 3 as acceptable, and 3 as good; this was in contrast to the treated group, where out of the 15 cases statics were deficient in 6, acceptable in 3, and good in 6 cases. Reviewing only those children over 2 years of age, statics were good in 8 cases. lmprovement was obtained in 7 out of 15 cases.

    Motor Coordination. Among the controls, moderate retardation was found in 8 out of 13 cases, and 2 were good. In the group treated with DMSO therapy, moderate retardation was found in 4 cases, and 9 were good. In those over 2 years of age, 1 out of 8 cases were classified as good. There was improvement in 7 out of 15 cases.

    Muscle Tone. The controls included 12 cases of rnarked or mild hypotonia and 1 normal case. In the treated group, after one year of DMSO treatment 12 out of 15 improved while 1 worsened. Among those more than 2 years of age, 5 out of 8 were normalized, 1 improved, 1 was unchanged, and in 1 case hypotonia increased.

    Sphincter Control. The control group showed no improvement in sphincter control. Two of the treated chudren began to control their sphincters. We must note that from the neurological point of view, there were no complications in either of the two groups.

    Laboratory Examinations. With respect to red blood corpuscles and hematocrit levels, in those more than 3½ years of age, the control group was found normal and the treated group presented only one case of 8 g-hemoglobin anemia before the DMSO therapy initiated. This was corrected during the treatment. The results of the laboratory examininations are shown in Table 2.

    The sedimentation rate in both groups presented temporary increases of up to 35 mrn/hour; these coincided, with the patterns for infections of the respiratory tract.

    The urine analysis was normal in alí cases. Hepatic tests were normal, with the exception of one of the treated patients, who had 14 units of alkaline phophatase; the remaining flocculation tests were also negative in this case.

    At the end of treatment, only 3 children had between 10 and 23 mm/hour; the rest were normal. The white corpuscle figures did not vary, and deviation to the lefi was occasional. Four children presented moderate lymphocytosis at the end of treatment as a consequence of the above-mentioned infections.

    The aminoacidemía exarninations were normal in alí cases. Amionaciduria was present in generalized form in 7 out of 11 controls and in 10 out of the 16 treated children.

    We did not observe any general complications IR relation to the treatment. In sorne of the children under 3½ years of age, transient hard but unpainfull zones appeared on the site of injection after the second or third series, but these disappeared during the month's rest period. In only one case it was necessary to continue the injections in the deltoid or the crural quadriceps. Not one patient had definite nodules (these might have made it necessary to suspend treatment). One case had a transíent fistula with exudate of the injected liquid, and two others developed bacterial abscesses, which were surgically treated.

Table 2

Results of Laboratory Examinations of Children with Trisomy-21
Aged Between 3 and 14 Years

Controls (11)
Before Treatment / After Treatment

Treated (16)
Before Treatment / After Treatment

Red Corpuscules

N / N

1 anemia / N

Hemoglobine

N / N

1 anemia / N

Hematocrit

N / N

1 anemia / N

White Corpuscles (transitory increse

   

Urine

N / N

N / N

Hepatic function

N / N

N / N

Aminoacidemia

N / N

N / N

Aminoaciduria

7 cases / 7 cases

7 cases / 7 cases

Commentary

    It seems to us that DMSO-acid therapy of children with trisomy-21 signifies an evident advance in the therapy of this syndrome. In those under 3½ years of age there was basically a greater receptiveness to outside stimuli; this gave them a greater interest in the surrounding environment, which in turn provoked greater activity and improved muscular tonus. The adaptive and social phases also showed a notable increase over what would usually be expected. Language, however remained almost stationary until a more advance age.

    The children's muscular coordination and statics in general also presented significant improvement, which in turn resulted in better sociability and less dependency, especially in those over 2 years of age.

    We know that the development quotient is not an index of the intelligence quotient, as it measures different functions of the nervous system. With increasing age, graphic irnprovement in drawing was observed, and the language and vocabulary of many children improved. Some even showed an improved intelligence quotient (which is possibly clouded or hidden by their limitations).

    We did not observe a relation between physical signs and the development quotient. We believe that the progress must be credited to the treatment. For the rnoment we dare not rnake a prognosis of the children`s future intellectual leveis. We also believe that if the parameters approach normality as a result of this treatment, this is already a positive result and we are on a good path with this therapy, as it is known that children with trisomy-21 tend to continue on the sarne deficient level, apart from complications. Moreover, in the first three years of life there is a tendency to regress due to their slow mental progress, which stabilizes at approxirnately the fourth year of life. We are aware that this clinical work includes rnany variables, which make the exact evaluation of the experience difficult. We also believe that to attain better results it is necessary to increase the number of children treated and the length of the treatmcnt to more than two years.

    In the treatrnent of some of our later patients (not related in this paper), we have administered higher doses, and up tilí now have obtained more favorable results.

    On the other hand, in two children who had to suspend the treatment for different reasons, progress made in the first weeks remained stagnant. This raises several question: How long should the treatment continue? At what stage of development does the patient's progress stabilize? The early initiation of therapy seems to be of great importance.

    We plan to continue our work with DMSO-amino acid therapy for at least two years.

    Is known that in Down's syndrome the frontal bbc and the cerebellum are both reduced in size. It would be interesting to know whether the treatment produces stimulation of these zones in the chudren, and if so, whether this stimulation in turn produces any anatomic or electroencephalographic change.

    Finally we want to emphasize that even though we have not arrived at an ideal treatment, we have reached a new stage in this difflcult field of medicine, in which there has been no other progress for several decades.

Acknowledgments

    We should like to express our gratitude to Dr. Javier Cox, Director of the Neurological Service of the Calvo Mackenna Children's Hospital for his valuable cooperation; to Dr. Viviana Mosca for her ophthalmological studies; to Mrs. Gladys Fausto, psychologist; and also to the Department of Cardiology of the Calvo Mackenna Hospital. We are ffirtherrnore deeply indebted to Mrs. Maria Gutierrez and Mis. Geraldine Armijo, our assistants during this investigation.

References

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2. Leake, C.D. 1967. Biological Actions of Dimethyl Sulfoxide. Ann. NY Acad. Sci. 141:1-671.
3. Jacob, S.W., M. Bischel & R.J. Herschler. 1964. Dimethyl Sulfoxide (DMSO): A new concept in pharmacotherapy. Current Therapy. Ref 6:134-135.
4. Jacob, S.W., E.E. Rosenbaum & D.C. Wood. 1971. Dimethyl Sulfoxide; Basic concepts of DMSO, Marcel Dekker, New York, N.Y.
5. Aspillaga, M.J. 1968. Exceso de autosomas. Mem. Oficiales XII Congr. Intern. Pediatría, Mexico 2:547.
6. Gardner, L.1. 1969. Endocrin and Genetic Viseases of Childhood. W.B. Saunders Co. Philadelphia, PA.
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8. Levinson, AA. Fridman & E. Stanps. 1955. Variability of rnongolism. Pediatries 16: 43.
9. Aspillaga, M.J. 1971. Consejo genético. Ren Med Clinic 99:171.

This article appeared in:

Biological Actions of Dimethyl Sulfoxide

Annals of the New York Academy of Science

Volume 243

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