THERAPY OF SQUINT IN DOWN SYNDROME SUBJECTS.
RESULTS ACCORDING TO THE LENGTH
OF DRUG TAKING: REPORT ON 125 CASES
Renato COCCHI,
neurologist and medical psychologist.
Summary
125 Down syndrome
Ss (F = 63 and M = 62; average age at first consultation = 76.57 +/- 5.52
months, range 5 - 271 months; cytodiagnoses distribution: 93.60 % pure trisomy
21; 4.00 % mosaicisms; 2.40 % translocations) affected by various degrees of
squint were assessed after different periods of drug therapy.
Although
the prescription has been individualized, all the Ss took, among the other
drugs, l-glutamine 90-250 mg; pyridoxine 125-150 mg; biotin 5 mg; diazepam 1-3
mg (daily doses). At T0 the squint distribution was as follows: slight: 33 Ss;
moderate: 10 Ss; marked: 74 Ss; severe: 8 Ss. At Tn (finaì assessments made
since up to 6 to up to 120 months of drug therapy) the distribution found was:
desappearance: 42 Ss; present only following antibiotic therapies for
respiratory infections: 28 Ss; present when the S is tired: 26 Ss; slight: 13
Ss; moderate: 3 S; marked: 12 Ss; severe: 1 Ss (Chi Square: 158.60; p <
.00025, 6 df). Possible explanations of the drugs action and choice are
suggested.
Key
words: Down's syndrome; squint; drug therapy; improvement; GABAergic drugs;
biotin.
Down's
syndrome
Mental
retardation
Drug therapy of stress reactions
Symptoms
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Congenital squint is very
frequently encountered in children suffering from Down's syndrome. Rates vary
from 21 to 44 % [1-3], being our own 27.91 % [4].
The causes
are unknown and merely hypothetical, but the frequent presence of this eyes
trouble in subjects affected by cerebral palsy (CP) - rated 37-60% in Harcourt
review [5] and reconfirmed 52.5-62%, according to more recent investigations
[6-9] - led Hugonnier and Hugonnier-Clayette to assert a common etiology [10].
Our
previous investigation aimed to correlate, in Down's syndrome subjects, risk
factors for CP such as prematurity and low birthweight and the presence or
absence of squint produced negative results [11].
Since
1979 I have been using low dosage drug treatment on children affected by Down's
syndrome. The rationale behind this therapy is that many Down's syndrome
symptoms are not due to the chromosomal anomaly itself, but to the organism's
response to endogenous metabolic stress.
This
stress is brought about by the 50% acceleration of all the metabolisms whose
control genes are found in chromosome 21 [12]. If 100% represents a metabolism
controlled by the 2 genes, as it normally happens, then this will become 150%
in the presence of 3 control genes as in trisomies.
This is
the well-known "dosage effect" which as already been demonstrated
regarding more than just one of these metabolisms [13-23].
One of
the unespected results of this therapeutic practice has been its beneficial
effect on nystagmus [24], confirmed also in non Down subjects [25], as well as
its effect on squint.
Given
these premises, a clinical survey was carried out in order to evaluate the
results obtained so far with Down subjects.
Subjects, materials and methods.
All the
medical records were re-examined of an unselected consecutive series of 470
Trisomy 21 patients, drawn from all over
The
records were extracted for all those who had shown visible evidence of squint
at the first visit and who had successively undergone the prescribed treatment
for at least 6 months.
At T0,
the initial squint evaluation, wich was purely clinical, was based on the
following criteria:
- light
(+), when deviation of the ocular axis went no further than halfway of its
possible movement towards the nose and, according to the parents, rarely was
not present;
-
moderate (++), as above but the position being permanent;
- marked
(+++) with ocular axis deviation tending to occupy also the second half of the
eyeball's possible movement towards the nose;
- severe
(++++), as above, but with fixed marked deviation.
At Tn,
final evaluation, 3 further distinctions were added:
- disappearance
(0);
- very
rare (--), as reported by the parents, present only after antibiotic therapies
mainly carried out following respiratory infections;
-
uncommon (-), as above and/or only present when the child is very tired.
Details
regarding sex, age at first consultation (months) and chromosomal diagnosis
were also taken from subjects with the required characteristics for this
investigation.
The
therapy carried out, despite being quite different from subject to subject
according to the differences in individual stress responses, always involved
(daily doses):
- l-glutamine: 90-250mg
- pyridoxine: 125-150mg;
- biotin:
2.5-5 mg;
-
diazepam: 1-3mg.
The
results taken pertained to the last visit made, i.e. results at six months
pertain to subjects having made only six months of drug therapy.
A
statistical analysis of the results was carried out using the non-parametric
Chi Square test.
Results.
Only 125
subjects were eligible for this study, out of 470. This group compri-sed 63
females and 62 males; sex ratio (M/F) = 98.41. Average age and SD at first
consultation: 76.57 +/- 5.52 months; range: 5-271.
The
chromosomal diagnoses were as follows:
pure
trisomy 21: 117 Ss = 93.60%;
mosaicisms:
5 Ss = 4.00 %;
translocations:
2 Ss = 1.60 %
unknown:
1 S = 0.80 %.
Results
are shown in table 1.
Table 1:
distribution of squint grades at T0 and Tn, according to the length (months) of
the drug taking.
|
|
|
|
Tn (months of drug taking) |
||||||||
|
Value |
T0 |
% |
6 |
7-12 |
13-24 |
25-36 |
37-60 |
61-84 |
85-120 |
totals |
% |
|
0 |
|
|
2 |
4 |
4 |
7 |
20 |
5 |
0 |
42 |
33.60 |
|
(--) |
|
|
1 |
1 |
2 |
8 |
15 |
1 |
0 |
28 |
22.40 |
|
(---) |
|
|
5 |
3 |
8 |
6 |
2 |
2 |
0 |
26 |
20.80 |
|
(+) |
33 |
26.40 |
6 |
2 |
1 |
0 |
0 |
2 |
2 |
13 |
10.40 |
|
(++) |
10 |
8.00 |
0 |
1 |
1 |
0 |
0 |
0 |
1 |
3 |
2.40 |
|
(***) |
74 |
59.20 |
3 |
2 |
5 |
1 |
1 |
0 |
0 |
12 |
9.60 |
|
(++++) |
8 |
6.40 |
0 |
0 |
0 |
0 |
1 |
0 |
0 |
1 |
0.80 |
|
Totals |
125 |
100.00 |
17 |
13 |
21 |
22 |
29 |
10 |
3 |
125 |
100.00 |
Chi Square: 158.60; df = 6;
p < .00025.
Discussion.
As regards selectional criteria for the
presence of squint, the symptom was only considered in those subjects who
showed evidence of it during the first visit.
The use of spectacles to correct squint was
not taken into account because young Down children do not tolerate them, and
more aged subjects with squint and spectacles are the proof that they had
scarce helpful by using them.
The distribution of chromosomal anomalies
parallels with Italian anä International limits [26-30].
The M/F ratio which was, on the contrary,
found to be equal in this selected male and female groups. This ratio differs
from that usually found regard trisomy 21, which in Italy ranges from 134/100
[27] to 136/100 calculated in the first 366 cases of this series [28].
As for the results, the casuistry here
presented, often backed up by photographic and filmed documentation, is by now
so strong that it is difficult to attribute all this to chance. If the
relationship between squint and CP in Down subjects is highly improbable [11],
the present results after drug therapy lead to a new suggestion. Convergent
squint in 21 trisomics, when not due to refraction problems, could be a symptom
of biochemical inbalance concerning oculomotor nuclei of the midbrain and of
the pons, vestibular area and reticular paramedian formation of the pons, added
to which, an interferring cerebellar dysfunction seems likely [31].
Such a dysfunction, ex adjuvantibus, seems
mainly due with GABA and glutamate.
In fact among the drugs used, glutamine is
the main precursor of glutamate and GABA in the brain [32]; pyridoxine, in the
form of pyridoxal-phosphate, is the co-factor of all the decarboxylases, as
well as the glutamic-acid-decarboxylase (GAD) [33]; diazepam is the sensitizer
of type A post-synaptic GABAergic receptor [34-36].
All three of these drugs have a precise
anti-stress function [37].
Pyridoxine and biotin have been found to be
strongly present in midbrain, pons and cerebellum in normal subjects [38]. This
last finding led me to suppose that their supply, in Down subjects, could
improve the neurochemical functioning of these areas. In my opinion, this seems
the least improbable explanation to justify the results obtained.
These same rusults also lead to infer that
when squint in Down subjects responds to an antistress therapy it is almost
certainly one of the many stress symptoms of the Down syndrome.
Biotin excluded, the medical correction of
squint does not involve the use of any different drugs other than those used as
basic for stress response correction in Down's syndrome. Apart from helping to
avoid any eventual surgical intervention on the eyes, the improvement of squint
in the Down child, by itself improves motor confidence as well as scholastic
performances.
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Paper presented at the First Europ. Conference on Mental Handicap and
Medical Care, Leeuwenhorst, april 21-24, 1991.
Printed on It. J. Intellect. Impair. 1991, 4: 9-14.
Author's address:
dr Renato COCCHI, via Rabbeno,3
42100 Reggio Emilia (Italy)
renatococchi@libero.it
Testo in italiano
Down's syndrome
Mental retardation
Drug therapy of stress reactions
Symptoms
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