THE BALANCE IN 230 DOWN SUBJECTS.

AN EVALUATION AFTER ONE-YEAR ANTISTRESS DRUG THERAPIES.

Renato COCCHI, neurologist and medical psychologist.

Abstract. 

Out of 383 Down Ss that who had an initial evaluation of their balance skills, 230 ( 122 M and 108 F; normal distribution of the chromosomal anomalies; average age at first consultation 67.69 +/- 56.03 months with 6-285 months range ), had an evaluation of the balance one year later, during antistress drug therapies. It resulted for a clean improvement of the balance that does not seem only due to the personal experience creditable to the growing age. Even in the Band age superior to 15 years (181-240 months) most subjects showed a more stable balance. At first watching, we cannot deny a specific drugs intervention (An improvement of the cerebellar function?), even if we need better investigate this result.

Key words: Down syndrome, balance, stress, age, antistress drug therapy, GABA, glutamate, cerebellum.

Italian translation

Down syndrome

Drug modulation of stress reactions.

Symptoms

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In a preliminary note on the troubles of the balance in the Down person (Cocchi, 1991) I made a neurophysiological, neuropathological, clinical and rehabilitative frame of reference where these troubles can take place and their treatment possibilities.

I mentioned there, at that moment, the dysfunction state of vestibular, mid-brain and pons, and cerebellar areas as possible promoters of the balance troubles. Felicioli and Moretti, 1984, asserted them as treatable..

As for me, the balance troubles in Downs are not secluded in a specific way from all motor skills of these subjects.

This clumsy and awkward motility, without any motor lesion, is enough similar to that of the children with mental retardation of other origin. On the other hand, the aspects of the balance control in Downs seem to have peculiar features, worthy of a punctual investigation. (Cocchi, 1991).

After a first epidemiological investigation on a cohort of 510 subjects (limit of my old data-base) (Cocchi, 2003), with evaluation after at least 6 months from the attainment of walking, out of the 383 cases reported in the preceding research I examined who had a second scoring of the balance after one-year antistress drug therapy.

Materials and methods.

This investigation used the clinical cards referring to 383 home reared and home living Downs as seen in outpatients' clinic by the present author, and object of the first investigation on the balance.(Cocchi, 2003). After one-year drug therapies I checked again tha balance skills, as compared to the preceding evaluation..

From the remaining records I collected:

- sex;

- chromosomal diagnosis;

- age at 1st consultation;

- age of the walking, if attained before the first examination, or before six months from the drugs taking (Group of not-pretreated Ss);

- age of the walking when attained after at least six months of drugs taking (Group of pretreated Ss);

- balance scoring after one year of drugs taking;

- the gradation of the balance as prevailing aspects, as it follows. I must remember that a child may anticipate a symptom of the upgrading condition, (usually the biking without support wheels) or may maintain a symptom of the downgrading condition (fear to be upon the basis of the scale to weigh).

(++++) a little uncertain walking; enlarged maintenance base; going upstairs downstairs by a simple footstep with the support of the adult or of the handrail; the child doesn't run, nor jumps, and he/she goes in panic if standing upon the basis of the scale to measure his/her weigh;

(+++) sure walking; less enlarged maintenance base; he/she climbs by alternating feet and go downstairs by simple footstep, without any support; awkward run; he/she doesn't know how to jump; and he/she goes in panic if standing upon the basis of the scale to measure his/her weigh;

(++) normal run or just a little awkward, with wavering of limbs; going upstairs and downstairs with alternating feet; jumps from at least two steps; he/she is biking with support wheels; no panic when he/she stands upon the basis of the scale to measure his/her weigh;

(+) like the preceding grade (++) but, as more, he/she is biking without support wheels. The balance trouble is nearly absent.

I elaborated the collected data by statistics for gender, chromosomal anomaly, and I classified them by 12-months-step age bands, and I evaluated them, when possible, with the Chi Square test.

Results.

The data of 230 subjects to whom pertain the clinical cards used for this investigation were reported in the following tables and graphics.

Tab. 1. Distribution for gender, for chromosomal diagnoses and age of the subjects who had balance scoring or at first examination, when already walking or walking since at least six months; Or 6-7 months after walking, when seen before walking at first consultation, and having a prescribed drug regimen.

	Ss		Percentage
Balance evaluation.	383		100.00 %
M	219		57.18 %
F	164		42.82 %
M/F ratio	133.54
Chromosomal diagnoses
Standard trisomia 21	347		90.60 %
Translocations	12		3.13 %
Mosaicisms	10	2.61 %
Only clinical diagnosis	14	3.66 %
Age at first consultation.
Average +/- SD (months)	83.53 +/- 71.23
Range (months)	6 - 506

The scored symptom has the usual male prevalence nearly overwhelming what found to the birth for Italian Down children (Camera and Mastroiacovo, 1984).

The distribution of the chromosomal anomalies does not differ from what known for both Italian and international Down populations.

Tab. 2: Balance scoring after one-year drugs therapy: Epidemiological data.

First balance evaluation	383		100.00 %
Re-evaluation after one-year therapy	230		60.05 %
Re-evaluation	230		100.00%
M	122		53.04 %
F	108		46.96 %
M/F ratio.	112.96 %
Chromosomal diagnoses
Standard trisomy 21	209		90.87 %
Translocations	9		3.92 %
Mosaicisms	7	3.04 %
Only clinical diagnosis	5	2.17 %
Age at first consultation.
Average +/- SD (months)	67.79 +/- 56.03
Range (months)	6 - 295

How we can see, only 230 Ss = 60.05% of whom had a first balance evaluation, had second scoring, after one-year drug therapies.

This subsample shows still a male prevalence, but it has a M/F ratio different from the usual, because decidedly reduced.

 Even here, the distribution of the chromosomal anomalies is close to what known for Italian and international Down populations.

The average age at first consultation is about 15-months lower, as compared to the whole sample of 383 Ss that had a first balance scoring. This is a fact easily to understand since the age range reduced of more than 200 months.

Tab. 3. Distribution for gender of the symptom "new scoring of balance troubles" according of its severity.

Gradation of the symptom	Ss no.	%
Severe trouble (++++)
M	0	0.00
F	1	0.43
Moderate trouble (+++)
M	50	21.74
F	52	22.61
Light trouble (++)
M	71	30.87
F	55	23.92
Nearly absent trouble (+)
M	1	0.43
F	0	0.00
Totals	230	100.00

Chi Square Test F vs M = 3.231 with three df and p = 0.488 NS.

The symptom distribution according to the gender after one year does not significantly differ. For what concerns the trouble ++ (a light trouble) and that + (a nearly absent trouble), we can observe male prevalence.

Tab. 4. Subjects not previously drug treated when I made the first scoring. Distribution of the balance trouble by age bands in months at first consultation and after one year. Scoring in the early age subjects, at least five months after attaining walking, if the age at first consultation preceded walking, or followed it until maximum four months (evaluation at five or more months after the acquisition of walking), and after 12 months, since the beginning of the drug therapy.

Total of Ss	334 Ss = 100.00 %, with first evaluation 183 Ss = 100.00%, with a second evaluation after one year
Age in months	Grade ++++ Ss No.		%	Grade +++ Ss. No.	%	Grade ++ Ss No.	%	Grade + Ss No.	%
13-24 (first eval.)	8		3.23	1	0.40	0	0.00	0	0.00
13-24 (final eval.)	0		0.00	0	0.00	0	0.00	0	0.00
25-36 (first eval.)	22		8.87	24	9.68	2	0.81	0	0.00
25-36 (final eval.)	0		0.00	8	4.37	1	0.55	0	0.00
37-48 (first eval.)	9		3.63	15	6.05	3	1.21	0	0.00
37-48 (final eval.)	0		0.00	16	8.74	21	11.48	1	0.55
49-60 (first eval.)	6		2.42	25	10.08	5	2.02	0	0.00
49-60 (final eval.)	0		0.00	10	5.46	7	3.83	1	0.55
61-72 (first eval.)	3		1.21	16	6.45	2	0.81	0	0.00
61-72 (final eval.)	1		0.55	9	4.92	16	8.74	1	0.55
73-84 (first eval.)	1		0.40	10	4.03	3	1.21	0	0.00
73-84 (final eval.)	0		0.00	0	0.00	13	7.10	0	0.00
85-96 (first eval.)	1		0.40	7	2.82	1	0.40	0	0.00
85-96 (final eval.)	0		0.00	1	0.55	11	6.01	0	0.00
97-108 (first eval.)		0	0.00	6	2.42	4	1.61	0	0.00
97-108 (final eval.)		0	0.00	2	1.09	4	2,19	0	0.00
109-120 (first eval.)		2	0.81	8	3.23	6	2.42	0	0.00
109-120 (final eval.)		0	0.00	2	1.09	6	3.28	0	0.00
121-132 (first eval.)		0	0.00	5	2.02	4	1.61	0	0.00
121-132 (final eval.)		0	0.00	5	2.73	12	6.56	0	0.00
133-144 (first eval.)		1	0.40	5	2.02	7	2.82	0	0.00
133-144 (final eval.)		0	0.00	0	0.00	7	3.83	0	0.00
145-156 (first eval.)		0	0.00	1	0.40	3	1.21	0	0.00
145-156 (final eval.)		0	0.00	1	0.55	8	4.37	1	0.55
157-168 (first eval.)		0	0.00	3	1.21	2	0.81	0	0.00
157-168 (final eval.)		0	0.00	1	0.55	3	1.64	0	0.00
169-180 (first eval.)		0	0.00	4	1.61	3	1.21	1	0.40
169-180 (final eval.)		0	0.00	0	0.00	2	1.09	0	0.00
181-240 (first eval.)		0	0.00	10	4.03	2	0.81	0	0.00
181-240 (final eval.)		0	0.00	3	1.64	6	3.28	0	0.00
241-360 (first eval.)		0	0.00	3	1.21	4	1.61	0	0.00
241-360 (final eval.)		0	0.00	0	0.00	3	1.64	0	0.00

Graph 1.

Now we may see from the graph 1, the more precarious balance condition diminished in an extraordinary way. Now it is represented only by one unique case (0.55%) in the age band between five and six years.

Graph 2.

A more favourable condition, but always with impairment, after one-year drugs therapy, together diminished, even if with not always a coherent time course. The small peak between 10 and 11 years could be a statistical artifact.

Graph 3.

 There is a definite increase of the less unfavourable balance condition with a peak in the 2-3 years. The result is always higher than the initial condition.

Graph 4.

As we can see, after a year of drugs therapy four Ss reached the nearly optimal level ( grade +), while there was only one before the therapy.

Even in the age band over 15 years (181-240 months) most Ss moved towards more stable balance condition. The same I could have said for the last age band (241-360 months), but the shortage in persons returned to check does not make it as valuable with a good approximation.

Tab. 5. Pretreated Ss. Distribution of the balance trouble in drug taking Ss, according to age bands, in months till 60 months, evaluated 6-7 months after starting of walking, and 12 months later.

Total of Ss -->		49 Ss = 100.00%, with initial evaluation; 47 Ss of which = 95.92, with evaluation one year later.
No. of Ss and %
Age, in months	13-24		%	25-36	%	37-48	%	49-60	%	61-72	%
++++ initial eval	2		4.08	26	57.14	4	8.16	1	2.04	0	0.00
++++ final eval.	0		0.00	1	2.04	0	0.00	0	0.00	0	0.00
+++ initial eval.	1		2.04	12	24.49	1	2.04	0	0.00	0	0.00
+++ final eval.	0		0.00	0	0.00	30	61.22	4	8.16	2	4.08
++ initial eval.	0		0.00	0	0.00	2	4.08	0	0.00	0	0.00
++ final eval.	0		0.00	1	2.04	8	16.33	0	0.00	0	0.00
+ initial eval.	0		0.00	0	0.00	0	0.00	0	0.00	0	0.00
+ final eval.	0		0.00	0	0.00	0	0.00	1	2.04	0	0.00

Graph 5

As we may see from the graph 5, the Ss already in treatment at least six months before they reached walking, one year later from the first balance scoring, most of them left this very unfavourable condition.

Graph 6.

The 47 subjects in drugs treatment from at least 6 monthes before they reached walking, moved in a still unfavourable situation, but with increased balance skills ( grade +++).

Graph 7.

 After one year, there is a clear displacement of the Ss, pretreated for at least 6 months before reaching walking, towards the balance condition with lighter deficits ( grade ++).

To that it is to add the appearance of a subject with nearly normal balance (grade +), after a year of drugs treatment.

Discussion.

I recall here that it is not easy to find literature on specific investigations of balance troubles in Down Ss. Internet (Google) and Medline from the 1960 to today did not help me about it. For what I know, it doesn't exist research on results on the balance in Down Ss treated by drugs therapy.

Felicioli and Moretti , 1984 find again, an altogether modest casuistry, a rate varying from 41.4% to 48.9 % and they thought that the smaller rate, related to Ss born five-years later, as the fruit of a wider and more precocious neuro-psychomotor rehabilitation. From it they deduced that the troubled balance is not stabilized, but "malleable", an opinion I completely agree.

In my casuistry on 16 Down persons with mosaicisms, I considered the motility as normal in 10 of them (Cocchi, 1996).

My previous epidemiological investigation, perhaps is the first wide casuistry, scored at first consultation according either to the chronological age either to the age of reaching walking (Cocchi, 2003).

Beyond a greater and significant general presence of the balance troubles in males, even that research could be debatable, because the evaluation at first consultation, implicated even a wider spontaneous experience and a longer period of neuro-psychomotor rehabilitation for the older subjects.

In spite of that, I found that after 10 years there were still 57 out 248 Ss (about 23%) with noticeable balance troubles. Did these subjects have scarce rehabilitation, or the trouble is not then fully resolvable?

Besides, the age, in its turn, works however as a great exercise or there exists even an excessive fear of losing the balance? Is it that, which would prevent in many Down subjects the reaching of a nearly optimal condition?

To this question we tried, in past, to give an answer, as regard to the acquisition of biking.

On 101 Down subjects of 10 or more years the investigation showed that about 54% of the sample did not bike. Among biking people, about 40% still did so by using even support wheels.

Biking seemed already then a difficult task for many Down Ss and learning it did fully correspond to the psychomotor level reached. (Cocchi and Favuto, 1994).

Now, it is not clear either if we can speak of a fear without any reason, or if in fact there are troubled signals, coming from the various receptors involved in the balance and/or from their processing.

The current research, on the effects on the balance of an antistress drugs therapy (for the used and their doses see: Cocchi, 1993) pointed up that in both groups under observation (not pretreated Down Ss and pretreated Down Ss) the course of the improvement does not parallel to its normal course.

There is an acceleration towards conditions of better stability, a fact poorly debatable, mainly in the group of the not pretreated Ss subjects at first scoring.

On the drug modulation of the stress reactions I send you again to the attempt of a rational explanation I gave in detailed way in an other article ( see: www.stress-cocchi.net/Drugs3-it.htm)

According to what I wrote then, the main focal points to act by drugs are:

- Increasing type A GABAergic inhibition;

- Decreasing type B GABAergic inhibition;

- Increasing the GAD action.

By themselves those interventions also induce:

- Decreasing of cortisol incretion and of the peripheral adrenergic compensation, by decreased activation of the hypothalamus-hypophysis-cortico-suprarenal axis (Buckingham, 1998; Schedlowski and Schmidt, 1996);

- Decreasing of the possible glutamate excess by an increased transformation of it into GABA.

Here, among the other drugs that allowed an individualized therapy, I used:

- A low dose benzodiazepine, to act on type A GABAergic receptors;

- A brain Ca-antagonist (carbamazepine) to reduce type B GABAergic inhibition (Crowder and Bradford, 1987).

- Pyridoxine acting as cofactor of all decarboxylases, GAD inclusive, as the decarboxylase that makes the transformation of glutamate into GABA.

It is possible that the cerebellar component of the balance has been favourably influenced by an antistress drugs therapy, but this aspect too deserves deeper investigations than the only two I did till now.

Conclusion.

The investigation on the Balance troubles in 230 Down subjects after one-year antistress drug therapy showed improvements. In the 183 not pretreated Ss, they does not parallel with the conditions of the same age balance development before the treatment, but are larger. Such ameliorations regarded even most Ss the of 15-21 years band age age, and this seems confirmation that with every probability it is a therapy effect.

References.

Buckingham JC. Stress and the hypothalamo-pituitary-immune axis. Int J Tissue Res. 1998, 20: 23-34.

Camera G., Mastroiacovo P.: Epidemiologia della sindrome di Down. In. Ce.Pi.M. (ed): Aspetti epidemiologici, genetici, clinici, riabilitativi e sociali della sindrome di Down. Ce.Pi.M., Genova 1984: 225-230

Cocchi R. Terapia farmacologica nella sindrome di Down: Inquadramento teorico. Riv.It. Disturbo Intellet. 1993, 6: 173-181. (www.stress-cocchi.net/Down14-it.htm).

Cocchi R. Forme a mosaico nella sindrome di Down: Indagine su 16 casi. Riv. It. Disturbo Intellet. 1996, 9: 107-116.

Cocchi R.: Difficoltà di controllo dell' equilibrio nel bambino Down (nota preliminare). Riv. It. Disturbo Intellet. 1991, 4: 267-270.

Cocchi R., Favuto M. Studio sull'uso della bicicletta nei Down di 10 o più anni. Riv. It. Disturbo Intellet. 1994, 7: 193-196

Cocchi R. Valutazione dell'equilibrio nel bambino Down. Indagine epidemiologica e clinica su 383 soggetti. (www.stress-cocchi.net/Down35-it.htm). Ottobre 2003.

Crowder J.M., Bradford H.F.: Common anticonvulsivants inhibits Ca++ uptake and amino acid neurotransmitter release in vitro. Epilepsia 1987, 28: 368-382.

Felicioli F., Moretti A.: Sviluppo motorio, comunicazionale linguistico ed evoluzioni dei livelli di apprendimento. In: Ce.Pi.M.: Aspetti epidemiologici, genetici, clinici, riabilitativi e sociali della Sindrome di Down. Ce.Pi.M., Genova 1984: 307-342. 

Schedlowski M, Schmidt RE. [Stress and immune system] Naturwissenschaften 1996, 83: 214-220 (originale in tedesco).

Immesso in Internet nell'ottobre 2003. Copyright by Renato Cocchi 2003.

Corrispondenza: dr Renato Cocchi, via Rabbeno, 3

42100 Reggio Emilia (Italy).

renatococchi@libero.it

Traduzione italiana

Down syndrome

Drug modulation of stress reactions.

Mental retardation

Symptoms

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